Please note: this site relies heavily on the use of javascript. Without a javascript-enabled browser, this site will not function correctly. Please enable javascript and reload the page, or switch to a different browser.
557  structures 1608  species 7  interactions 2433  sequences 35  architectures

Family: RuBisCO_large (PF00016)

Summary: Ribulose bisphosphate carboxylase large chain, catalytic domain

Pfam includes annotations and additional family information from a range of different sources. These sources can be accessed via the tabs below.

This is the Wikipedia entry entitled "RuBisCO". More...

RuBisCO Edit Wikipedia article

Ribulose-1,5-bisphosphate carboxylase oxygenase
Figure 1. A 3d cartoon depiction of the activated RuBisCO from spinach in open form with active site accessible. The active site Lys175 residues are marked in pink, and a close-up of the residue is provided to the right for one of the monomers composing the enzyme.
EC number
CAS number 9027-23-0
IntEnz IntEnz view
ExPASy NiceZyme view
MetaCyc metabolic pathway
PRIAM profile
PDB structures RCSB PDB PDBe PDBsum
Gene Ontology AmiGO / QuickGO

Ribulose-1,5-bisphosphate carboxylase/oxygenase, commonly known by the abbreviations RuBisCO, RuBPCase, or RuBPco, is an enzyme involved in the first major step of carbon fixation, a process by which atmospheric carbon dioxide is converted by plants and other photosynthetic organisms to energy-rich molecules such as glucose. In chemical terms, it catalyzes the carboxylation of ribulose-1,5-bisphosphate (also known as RuBP). It is probably the most abundant enzyme on Earth.[1][2]

Vs. alternative carbon fixation pathways

RuBisCO is important biologically because it catalyzes the primary chemical reaction by which inorganic carbon enters the organic biosphere. While many autotrophic bacteria and archaea fix carbon via the reductive acetyl CoA pathway, the 3-hydroxypropionate cycle, or the reverse Krebs cycle, these pathways are relatively smaller contributors to global carbon fixation than that catalyzed by RuBisCO. Phosphoenolpyruvate carboxylase, unlike RuBisCO, only temporarily fixes carbon. Reflecting its importance, RuBisCO is the most abundant protein in leaves, accounting for 50% of soluble leaf protein in C3 plants (20–30% of total leaf nitrogen) and 30% of soluble leaf protein in C4 plants (5–9% of total leaf nitrogen).[2] Given its important role in the biosphere, the genetic engineering of RuBisCO in crops is of continuing interest (see below).


In plants, algae, cyanobacteria, and phototrophic and chemoautotrophic proteobacteria, the enzyme usually consists of two types of protein subunit, called the large chain (L, about 55,000 Da) and the small chain (S, about 13,000 Da). The large-chain gene (rbcL) is encoded by the chloroplast DNA in plants.[3] There are typically several related small-chain genes in the nucleus of plant cells, and the small chains are imported to the stromal compartment of chloroplasts from the cytosol by crossing the outer chloroplast membrane.[4][5] The enzymatically active substrate (ribulose 1,5-bisphosphate) binding sites are located in the large chains that form dimers as shown in Figure 1 (above, right) in which amino acids from each large chain contribute to the binding sites. A total of eight large-chains (= 4 dimers) and eight small chains assemble into a larger complex of about 540,000 Da.[6] In some proteobacteria and dinoflagellates, enzymes consisting of only large subunits have been found.[7]

Magnesium ions (Mg2+
) are needed for enzymatic activity. Correct positioning of Mg2+
in the active site of the enzyme involves addition of an "activating" carbon dioxide molecule (CO2) to a lysine in the active site (forming a carbamate).[8] Mg2+ operates by driving deprotonation of the Lys210 residue, causing the Lys residue to rotate by 120 degrees to the trans conformer, decreasing the distance between the nitrogen of Lys and the carbon of CO2. The close proximity allows for the formation of a covalent bond, resulting in the carbamate.[9] Mg2+ is first enabled to bind to the active site by the rotation of His335 to an alternate conformation. Mg2+ is then coordinated by the His residues of the active site (His300, His302, His335), and is partially neutralized by the coordination of three water molecules and their conversion to OH (Figure 2).[9] This coordination results in an unstable complex, but produces a favorable environment for the binding of Mg2+. Formation of the carbamate is favored by an alkaline pH. The pH and the concentration of magnesium ions in the fluid compartment (in plants, the stroma of the chloroplast[10]) increases in the light. The role of changing pH and magnesium ion levels in the regulation of RuBisCO enzyme activity is discussed below. Once the carbamate is formed, His335 finalizes the activation by returning back to its initial position through thermal fluctuation.[9]

RuBisCO large chain,
catalytic domain
Symbol RuBisCO_large
Pfam PF00016
InterPro IPR000685
SCOP 3rub
CDD cd08148
RuBisCO, N-terminal domain
Symbol RuBisCO_large_N
Pfam PF02788
InterPro IPR017444
SCOP 3rub
RuBisCO, small chain
Symbol RuBisCO_small
Pfam PF00101
InterPro IPR000894
SCOP 3rub
CDD cd03527

Enzymatic activity

Figure 3. Overview of the Calvin cycle and carbon fixation

As shown in Figure 2 (left), RuBisCO is one of many enzymes in the Calvin cycle.


During carbon fixation, the substrate molecules for RuBisCO are ribulose-1,5-bisphosphate and carbon dioxide (distinct from the "activating" carbon dioxide).[11] RuBisCO also catalyses a reaction between ribulose-1,5-bisphosphate and molecular oxygen (O
) instead of carbon dioxide (CO2).

Distinguishing between substrates

Due to the overall neutral charge and lack of dipole in both substrates, discriminating between and binding the substrates at the active site rely on the interaction between the quadrupole moments of both substrates and a high electrostatic field gradient from the enzyme.[9] This gradient is established by the dimer form of the minimally active RuBisCO, which with its two components provides a combination of oppositely charged domains required for the enzyme’s interaction with O2 and CO2. These conditions help explain the low turnover rate found in RuBisCO: In order to increase the strength of the electric field necessary for sufficient interaction with the substrates’ quadrupole moments, the C- and N- terminal segments of the enzyme must be closed off, allowing the active site to be isolated from the solvent and lowering the dielectric constant.[12] This isolation has a significant entropic cost, and results in the poor turnover rate.


When carbon dioxide is the substrate, the product of the carboxylase reaction is a highly unstable six-carbon phosphorylated intermediate known as 3-keto-2-carboxyarabinitol-1,5-bisphosphate, which decays virtually instantaneously into two molecules of glycerate-3-phosphate. The extremely unstable molecule created by the initial carboxylation was unknown until 1988, when it was isolated. The 3-phosphoglycerate can be used to produce larger molecules such as glucose. Also, Rubisco side activities can lead to useless or inhibitory by-products; one such product is xylulose-1,5-bisphosphate, which inhibits Rubisco activity.[13]

When molecular oxygen is the substrate, the products of the oxygenase reaction are phosphoglycolate and 3-phosphoglycerate. Phosphoglycolate is recycled through a sequence of reactions called photorespiration, which involves enzymes and cytochromes located in the mitochondria and peroxisomes (this is a case of metabolite repair). In this process, two molecules of phosphoglycolate are converted to one molecule of carbon dioxide and one molecule of 3-phosphoglycerate, which can reenter the Calvin cycle. Some of the phosphoglycolate entering this pathway can be retained by plants to produce other molecules such as glycine. At ambient levels of carbon dioxide and oxygen, the ratio of the reactions is about 4 to 1, which results in a net carbon dioxide fixation of only 3.5. Thus, the inability of the enzyme to prevent the reaction with oxygen greatly reduces the photosynthetic capacity of many plants. Some plants, many algae, and photosynthetic bacteria have overcome this limitation by devising means to increase the concentration of carbon dioxide around the enzyme, including C4 carbon fixation, crassulacean acid metabolism, and the use of pyrenoid.

Rate of enzymatic activity

Some enzymes can carry out thousands of chemical reactions each second. However, RuBisCO is slow, being able to fix only 3-10 carbon dioxide molecules each second per molecule of enzyme.[14] The reaction catalyzed by RuBisCO is, thus, the primary rate-limiting factor of the Calvin cycle during the day. Nevertheless, under most conditions, and when light is not otherwise limiting photosynthesis, the speed of RuBisCO responds positively to increasing carbon dioxide concentration. However, our descriptive knowledge will become more usable when we can translate them into quantitative models that can enable us to calculate the outcome of the reaction under a given condition. Since RubisCO reacts with RuBP (ribulose 1,5 bisphosphate) first to produce enediol and next with CO2 that after some intermediate changes produces PGA (3-phosphoglycerate), a biochemical model is developed [15] to represent the effects of these steps quantitatively. Since carboxylation or fixation of CO2 is possible only after the synthesis of enediol, thus it is suggested that the role of RubisCO is to produce enediol that is carboxylase and oxygenase (EnCO). Accordingly, RubisCO is called enolase-phosphoglycerase (EPGase) since it is neither carboxylase nor oxygenase.

Regulation of its enzymatic activity

RuBisCO is usually only active during the day as ribulose 1,5-bisphosphate is not regenerated in the dark. This is due to the regulation of several other enzymes in the Calvin cycle. In addition, the activity of RuBisCO is coordinated with that of the other enzymes of the Calvin cycle in several ways.

Regulation by ions

Upon illumination of the chloroplasts, the pH of the stroma rises from 7.0 to 8.0 because of the proton (hydrogen ion, H+
) gradient created across the thylakoid membrane.[16] At the same time, magnesium ions (Mg2+
) move out of the thylakoids, increasing the concentration of magnesium in the stroma of the chloroplasts. RuBisCO has a high optimal pH (can be >9.0, depending on the magnesium ion concentration) and, thus, becomes "activated" by the addition of carbon dioxide and magnesium to the active sites as described above.

Regulation by RuBisCO activase

In plants and some algae, another enzyme, RuBisCO activase, is required to allow the rapid formation of the critical carbamate in the active site of RuBisCO.[17][18] RuBisCO activase is required because the ribulose 1,5-bisphosphate (RuBP) substrate binds more strongly to the active sites lacking the carbamate and markedly slows down the "activation" process. In the light, RuBisCO activase promotes the release of the inhibitory (or — in some views — storage) RuBP from the catalytic sites. Activase is also required in some plants (e.g., tobacco and many beans) because, in darkness, RuBisCO is inhibited (or protected from hydrolysis) by a competitive inhibitor synthesized by these plants, a substrate analog 2-Carboxy-D-arabitinol 1-phosphate (CA1P).[19] CA1P binds tightly to the active site of carbamylated RuBisCO and inhibits catalytic activity. In the light, RuBisCO activase also promotes the release of CA1P from the catalytic sites. After the CA1P is released from RuBisCO, it is rapidly converted to a non-inhibitory form by a light-activated CA1P-phosphatase. Finally, once every several hundred reactions, the normal reactions with carbon dioxide or oxygen are not completed, and other inhibitory substrate analogs are formed in the active site. Once again, RuBisCO activase can promote the release of these analogs from the catalytic sites and maintain the enzyme in a catalytically active form. The properties of activase limit the photosynthetic potential of plants at high temperatures.[20] CA1P has also been shown to keep RuBisCO in a conformation that is protected from proteolysis.[21] At high temperatures, RuBisCO activase aggregates and can no longer activate RuBisCO. This contributes to the decreased carboxylating capacity observed during heat stress.[22]

Regulation by ATP/ADP and stromal reduction/oxidation state through the activase

The removal of the inhibitory RuBP, CA1P, and the other inhibitory substrate analogs by activase requires the consumption of ATP. This reaction is inhibited by the presence of ADP, and, thus, activase activity depends on the ratio of these compounds in the chloroplast stroma. Furthermore, in most plants, the sensitivity of activase to the ratio of ATP/ADP is modified by the stromal reduction/oxidation (redox) state through another small regulatory protein, thioredoxin. In this manner, the activity of activase and the activation state of RuBisCO can be modulated in response to light intensity and, thus, the rate of formation of the ribulose 1,5-bisphosphate substrate.[23]

Regulation by phosphate

In cyanobacteria, inorganic phosphate (Pi) participates in the co-ordinated regulation of photosynthesis. Pi binds to the RuBisCO active site and to another site on the large chain where it can influence transitions between activated and less active conformations of the enzyme. Activation of bacterial RuBisCO might be particularly sensitive to Pi levels, which can act in the same way as RuBisCO activase in higher plants.[24]

Regulation by carbon dioxide

Since carbon dioxide and oxygen compete at the active site of RuBisCO, carbon fixation by RuBisCO can be enhanced by increasing the carbon dioxide level in the compartment containing RuBisCO (chloroplast stroma). Several times during the evolution of plants, mechanisms have evolved for increasing the level of carbon dioxide in the stroma (see C4 carbon fixation). The use of oxygen as a substrate appears to be a puzzling process, since it seems to throw away captured energy. However, it may be a mechanism for preventing overload during periods of high light flux. This weakness in the enzyme is the cause of photorespiration, such that healthy leaves in bright light may have zero net carbon fixation when the ratio of O
to CO2 reaches a threshold at which oxygen is fixed instead of carbon. This phenomenon is primarily temperature-dependent. High temperature decreases the concentration of CO2 dissolved in the moisture in the leaf tissues. This phenomenon is also related to water stress. Since plant leaves are evaporatively cooled, limited water causes high leaf temperatures. C4 plants use the enzyme PEP carboxylase initially, which has a higher affinity for CO2. The process first makes a 4-carbon intermediate compound, which is shuttled into a site of C3 photosynthesis then de-carboxylated, releasing CO2 to boost the concentration of CO2, hence the name C4 plants.

Crassulacean acid metabolism (CAM) plants keep their stomata (on the underside of the leaf) closed during the day, which conserves water but prevents the light-independent reactions (a.k.a. the Calvin Cycle) from taking place, since these reactions require CO2 to pass by gas exchange through these openings. Evaporation through the upper side of a leaf is prevented by a layer of wax.

Genetic engineering

Since RuBisCO is often rate-limiting for photosynthesis in plants, it may be possible to improve photosynthetic efficiency by modifying RuBisCO genes in plants to increase catalytic activity and/or decrease oxygenation rates.[25] This could improve biosequestration of CO2 and be both an important climate change strategy and a strategy to increase crop yields.[26] Approaches under investigation include transferring RuBisCO genes from one organism into another organism, engineering Rubisco activase from thermophilic cyanobacteria into temperature sensitive plants, increasing the level of expression of RuBisCO subunits, expressing RuBisCO small chains from the chloroplast DNA, and altering RuBisCO genes to increase specificity for carbon dioxide or otherwise increase the rate of carbon fixation.[27][28] Although, as the levels of CO2 rise, efforts to increase specificity for CO2 may be unnecessary.

Mutagenesis in plants

In general, site-directed mutagenesis of RuBisCO has been mostly unsuccessful,[26] though mutated forms of the protein have been achieved in tobacco plants with subunit C4 species,[29] and a RuBisCO with more C4-like kinetic characteristics have been attained in rice via nuclear transformation.[30]

One avenue is to introduce RuBisCO variants with naturally high specificity values such as the ones from the red alga Galdieria partita into plants. This may improve the photosynthetic efficiency of crop plants, although possible negative impacts have yet to be studied.[31] Advances in this area include the replacement of the tobacco enzyme with that of the purple photosynthetic bacterium Rhodospirillum rubrum.[32] In 2014, two transplastomic tobacco lines with functional RuBisCO from the cyanobacterium Synechococcus elongatus PCC7942 (Se7942) were created by replacing the RuBisCO with the large and small subunit genes of the Se7942 enzyme, in combination with either the corresponding Se7942 assembly chaperone, RbcX, or an internal carboxysomal protein, CcmM35. Both mutants had increased CO2 fixation rates when measured as carbon molecules per RuBisCO. However, the mutant plants grew more slowly than wild-type.[33]

A recent theory explores the trade-off between the relative specificity (i.e., ability to favour CO2 fixation over O
incorporation, which leads to the energy-wasteful process of photorespiration) and the rate at which product is formed. The authors conclude that RuBisCO may actually have evolved to reach a point of 'near-perfection' in many plants (with widely varying substrate availabilities and environmental conditions), reaching a compromise between specificity and reaction rate.[34]

Since photosynthesis is the single most effective natural regulator of carbon dioxide in the Earth's atmosphere, a biochemical model of RuBisCO reaction is used as the core module of climate change models. Thus, a correct model of this reaction is essential to the basic understanding of the relations and interactions of environmental models. A new theory and model of the biochemical reaction of photosynthesis and the drawbacks of today's most widely used model of photosynthesis is discussed in volume 29 of Advances in Photosynthesis and Respiration.[35]

Expression in bacterial hosts

There currently are very few effective methods for expressing functional plant RuBisCO in bacterial hosts for genetic manipulation studies. This is largely due to RuBisCO's requirement of complex cellular machinery for its biogenesis and metabolic maintenance including the nuclear-encoded RbcS subunits, which are typically imported into chloroplasts as unfolded proteins.[36][37] Furthermore, sufficient expression and interaction with RuBisCO activase are major challenges as well.[38] One successful method for expression of RuBisCO in E. coli involves the coexpression of multiple chloroplast chaperones, though this has only been shown in Arabidopsis thaliana.[39]

Depletion in proteomic studies

Due to its high abundance in plants (generally 40% of the total protein content), RuBisCO often impedes analysis of important signaling proteins such as transcription factors, kinases, and regulatory proteins found in lower abundance (10-100 molecules per cell) within plants.[40] For example, using mass spectrometry on plant protein mixtures would result in multiple intense RuBisCO subunit peaks that interfere and hide those of other proteins.

Recently, one efficient method for precipitating out RuBisCO involves the usage of protamine sulfate solution.[41] Other existing methods for depleting RuBisCO and studying lower abundance proteins include fractionation techniques with calcium and phytate,[42] gel electrophoresis with polyethylene glycol,[43][44] affinity chromatography,[45][46] and aggregation using DTT,[47] though these methods are more time-consuming and less efficient when compared to protamine sulfate precipitation.[40]

Phylogenetic studies

The chloroplast gene rbcL, which codes for the large subunit of RuBisCO has been widely used as an appropriate locus for analysis of phylogenetics in plant taxonomy.[48]

Evolution of RuBisCO

With the evolution of the C4-fixation pathway in certain species of plants, C3 RuBisCO evolved to have faster turnover of CO2 in exchange for lower specificity as a result of the greater localization of CO2 from the mesophyll cells into the bundle sheath cells.[49] This was achieved through enhancement of conformational flexibility of the “open-closed” transition in the Calvin Cycle. Laboratory-based phylogenetic studies have shown that this evolution was constrained by the trade-off between stability and activity brought about by the series of necessary mutations for C4 RuBisCO.[50] Moreover, in order to sustain the destabilizing mutations, the evolution to C4 RuBisCO was preceded by a period in which mutations granted the enzyme increased stability, establishing a buffer to sustain and maintain the mutations required for C4 RuBisCO. To assist with this buffering process, the newly-evolved enzyme was found to have further developed a series of stabilizing mutations. While RuBisCO has always been accumulating new mutations, most of these mutations that have survived have not had significant effects on protein stability. The destabilizing C4 mutations on RuBisCO has been sustained by environmental pressures such as low CO2 concentrations, requiring a sacrifice of stability for new adaptive functions.[50]

History of the term

The term "RuBisCO" was coined humorously in 1979, by David Eisenberg at a seminar honouring the retirement of the early, prominent RuBisCO researcher, Sam Wildman, and also alluded to the snack food trade name "Nabisco" in reference to Wildman's attempts to create an edible protein supplement from tobacco leaves.[51]

See also


  1. ^ Cooper, Geoffrey M. (2000). "10.The Chloroplast Genome". The Cell: A Molecular Approach (2nd ed.). Washington, D.C: ASM Press. ISBN 0-87893-106-6. , one of the subunits of ribulose bisphosphate carboxylase (rubisco) is encoded by chloroplast DNA. Rubisco is the critical enzyme that catalyzes the addition of CO2 to ribulose-1,5-bisphosphate during the Calvin cycle (see Figure 2.39). It is also thought to be the single most abundant protein on Earth, so it is noteworthy that one of its subunits is encoded by the chloroplast genome. 

    Dhingra A, Portis AR, Daniell H (April 2004). "Enhanced translation of a chloroplast-expressed RbcS gene restores small subunit levels and photosynthesis in nuclear RbcS antisense plants". Proceedings of the National Academy of Sciences of the United States of America. 101 (16): 6315–20. Bibcode:2004PNAS..101.6315D. doi:10.1073/pnas.0400981101. PMC 395966Freely accessible. PMID 15067115. (Rubisco) is the most prevalent enzyme on this planet, accounting for 30–50% of total soluble protein in the chloroplast; 
  2. ^ a b Feller U, Anders I, Mae T (2008). "Rubiscolytics: fate of Rubisco after its enzymatic function in a cell is terminated". Journal of Experimental Botany. 59 (7): 1615–24. doi:10.1093/jxb/erm242. PMID 17975207. 
  3. ^ (Entrez GeneID: )
  4. ^ Dhingra A, Portis AR, Daniell H (April 2004). "Enhanced translation of a chloroplast-expressed RbcS gene restores small subunit levels and photosynthesis in nuclear RbcS antisense plants". Proceedings of the National Academy of Sciences of the United States of America. 101 (16): 6315–20. Bibcode:2004PNAS..101.6315D. doi:10.1073/pnas.0400981101. PMC 395966Freely accessible. PMID 15067115. 
  5. ^ Arabidopsis thaliana has four RuBisCO small chain genes. The pattern of how large chains and small chains assemble is illustrated in Figure 3 (right).
    Yoon M, Putterill JJ, Ross GS, Laing WA (April 2001). "Determination of the relative expression levels of rubisco small subunit genes in Arabidopsis by rapid amplification of cDNA ends". Analytical Biochemistry. 291 (2): 237–44. doi:10.1006/abio.2001.5042. PMID 11401297. 
  6. ^ Stryer, Lubert; Berg, Jeremy Mark; Tymoczko, John L. (2002). "20. The Calvin Cycle and the Pentose Phosphate Pathway". Biochemistry (5th ed.). San Francisco: W.H. Freeman. ISBN 0-7167-3051-0. Figure 20.3. Structure of Rubisco. (Color-coded ribbon diagram) 
    Figure 1 (on this page, near top) shows another view of the structure.
  7. ^ The structure of RuBisCO from the photosynthetic bacterium Rhodospirillum rubrum has been determined by X-ray crystallography, see: PDB: 9RUB​. A comparison of the structures of eukaryotic and bacterial RuBisCO is shown in the Protein Data Bank feature article on Rubisco.
  8. ^ Molecular Cell Biology, 4th edition, by Harvey Lodish, Arnold Berk, S. Lawrence Zipursky, Paul Matsudaira, David Baltimore and James E. Darnell. Published by W. H. Freeman & Co. (2000) New York. Online textbook. Figure 16-48 shows a structural model of the active site, including the involvement of magnesium. The Protein Data Bank feature article on RuBisCO also includes a model of magnesium at the active site.
  9. ^ a b c d Stec B (November 2012). "Structural mechanism of RuBisCO activation by carbamylation of the active site lysine". Proceedings of the National Academy of Sciences of the United States of America. 109 (46): 18785–90. Bibcode:2012PNAS..10918785S. doi:10.1073/pnas.1210754109. PMC 3503183Freely accessible. PMID 23112176. 
  10. ^ The Lodish textbook describes the localization of RuBisCO to the stromal space of chloroplasts. Figure 17-7 illustrates how RuBisCO small subunits move into the chloroplast stroma and assemble with the large subunits.
  11. ^ The chemical reactions catalyzed by RuBisCO are described in the online Biochemistry textbook by Stryer et al.
  12. ^ Satagopan S, Spreitzer RJ (July 2008). "Plant-like substitutions in the large-subunit carboxy terminus of Chlamydomonas Rubisco increase CO2/O2 specificity". BMC Plant Biology. 8: 85. doi:10.1186/1471-2229-8-85. PMID 18664299. 
  13. ^ Pearce FG (November 2006). "Catalytic by-product formation and ligand binding by ribulose bisphosphate carboxylases from different phylogenies". The Biochemical Journal. 399 (3): 525–34. doi:10.1042/BJ20060430. PMC 1615894Freely accessible. PMID 16822231. 
  14. ^ Ellis RJ (January 2010). "Biochemistry: Tackling unintelligent design". Nature. 463 (7278): 164–5. Bibcode:2010Natur.463..164E. doi:10.1038/463164a. PMID 20075906. 
  15. ^ Farazdaghi H (February 2011). "The single-process biochemical reaction of Rubisco: a unified theory and model with the effects of irradiance, CO₂ and rate-limiting step on the kinetics of C₃ and C₄ photosynthesis from gas exchange". Bio Systems. 103 (2): 265–84. doi:10.1016/j.biosystems.2010.11.004. PMID 21093535. 
  16. ^ Figure 20.14 in the textbook by Stryer et al. illustrates the light-dependent movement of hydrogen and magnesium ions that are important for Light Regulation of the Calvin Cycle. The movement of protons into thylakoids is driven by light and is fundamental to ATP synthesis in chloroplasts.
  17. ^ Portis AR (2003). "Rubisco activase - Rubisco's catalytic chaperone". Photosynthesis Research. 75 (1): 11–27. doi:10.1023/A:1022458108678. PMID 16245090. 
  18. ^ Jin SH, Jiang DA, Li XQ, Sun JW (August 2004). "Characteristics of photosynthesis in rice plants transformed with an antisense Rubisco activase gene". Journal of Zhejiang University. Science. 5 (8): 897–9. doi:10.1631/jzus.2004.0897. PMID 15236471. 
  19. ^ Andralojc PJ, Dawson GW, Parry MA, Keys AJ (December 1994). "Incorporation of carbon from photosynthetic products into 2-carboxyarabinitol-1-phosphate and 2-carboxyarabinitol". The Biochemical Journal. 304 ( Pt 3) (3): 781–6. PMC 1137402Freely accessible. PMID 7818481. 
  20. ^ Crafts-Brandner SJ, Salvucci ME (November 2000). "Rubisco activase constrains the photosynthetic potential of leaves at high temperature and CO2". Proceedings of the National Academy of Sciences of the United States of America. 97 (24): 13430–5. Bibcode:2000PNAS...9713430C. doi:10.1073/pnas.230451497. PMC 27241Freely accessible. PMID 11069297. 
  21. ^ Khan S, Andralojc PJ, Lea PJ, Parry MA (December 1999). "2'-carboxy-D-arabitinol 1-phosphate protects ribulose 1, 5-bisphosphate carboxylase/oxygenase against proteolytic breakdown". European Journal of Biochemistry. 266 (3): 840–7. doi:10.1046/j.1432-1327.1999.00913.x. PMID 10583377. 
  22. ^ Salvucci ME, Osteryoung KW, Crafts-Brandner SJ, Vierling E (November 2001). "Exceptional sensitivity of Rubisco activase to thermal denaturation in vitro and in vivo". Plant Physiology. 127 (3): 1053–64. doi:10.1104/pp.010357. PMC 129275Freely accessible. PMID 11706186. 
  23. ^ Zhang N, Kallis RP, Ewy RG, Portis AR (March 2002). "Light modulation of Rubisco in Arabidopsis requires a capacity for redox regulation of the larger Rubisco activase isoform". Proceedings of the National Academy of Sciences of the United States of America. 99 (5): 3330–4. Bibcode:2002PNAS...99.3330Z. doi:10.1073/pnas.042529999. PMC 122518Freely accessible. PMID 11854454. 
  24. ^ Marcus Y, Gurevitz M (October 2000). "Activation of cyanobacterial RuBP-carboxylase/oxygenase is facilitated by inorganic phosphate via two independent mechanisms". European Journal of Biochemistry. 267 (19): 5995–6003. doi:10.1046/j.1432-1327.2000.01674.x. PMID 10998060. 
  25. ^ Spreitzer RJ, Salvucci ME (2002). "Rubisco: structure, regulatory interactions, and possibilities for a better enzyme". Annual Review of Plant Biology. 53: 449–75. doi:10.1146/annurev.arplant.53.100301.135233. PMID 12221984. 
  26. ^ a b Furbank, Robert T.; Quick, W. Paul; Sirault, Xavier R.R. "Improving photosynthesis and yield potential in cereal crops by targeted genetic manipulation: Prospects, progress and challenges". Field Crops Research. 182: 19–29. doi:10.1016/j.fcr.2015.04.009. 
  27. ^ Parry MA, Andralojc PJ, Mitchell RA, Madgwick PJ, Keys AJ (May 2003). "Manipulation of Rubisco: the amount, activity, function and regulation". Journal of Experimental Botany. 54 (386): 1321–33. doi:10.1093/jxb/erg141. PMID 12709478. 
  28. ^ Ogbaga CC, Stepien P, Athar HU, Ashraf M (September 2017). "Engineering Rubisco activase from thermophilic cyanobacteria into high-temperature sensitive plants". Critical Reviews in Biotechnology: 1–14. doi:10.1080/07388551.2017.1378998. PMID 28937283. 
  29. ^ Whitney SM, Sharwood RE, Orr D, White SJ, Alonso H, Galmés J (August 2011). "Isoleucine 309 acts as a C4 catalytic switch that increases ribulose-1,5-bisphosphate carboxylase/oxygenase (rubisco) carboxylation rate in Flaveria". Proceedings of the National Academy of Sciences of the United States of America. 108 (35): 14688–93. Bibcode:2011PNAS..10814688W. doi:10.1073/pnas.1109503108. PMC 3167554Freely accessible. PMID 21849620. 
  30. ^ Ishikawa C, Hatanaka T, Misoo S, Miyake C, Fukayama H (July 2011). "Functional incorporation of sorghum small subunit increases the catalytic turnover rate of Rubisco in transgenic rice". Plant Physiology. 156 (3): 1603–11. doi:10.1104/pp.111.177030. PMC 3135941Freely accessible. PMID 21562335. 
  31. ^ Whitney SM, Andrews TJ (December 2001). "Plastome-encoded bacterial ribulose-1,5-bisphosphate carboxylase/oxygenase (RubisCO) supports photosynthesis and growth in tobacco". Proceedings of the National Academy of Sciences of the United States of America. 98 (25): 14738–43. Bibcode:2001PNAS...9814738W. doi:10.1073/pnas.261417298. PMC 64751Freely accessible. PMID 11724961. 
  32. ^ John Andrews T, Whitney SM (June 2003). "Manipulating ribulose bisphosphate carboxylase/oxygenase in the chloroplasts of higher plants". Archives of Biochemistry and Biophysics. 414 (2): 159–69. doi:10.1016/S0003-9861(03)00100-0. PMID 12781767. 
  33. ^ Lin MT, Occhialini A, Andralojc PJ, Parry MA, Hanson MR (September 2014). "A faster Rubisco with potential to increase photosynthesis in crops". Nature. 513 (7519): 547–50. Bibcode:2014Natur.513..547L. doi:10.1038/nature13776. PMC 4176977Freely accessible. PMID 25231869. 
  34. ^ Tcherkez GG, Farquhar GD, Andrews TJ (May 2006). "Despite slow catalysis and confused substrate specificity, all ribulose bisphosphate carboxylases may be nearly perfectly optimized". Proceedings of the National Academy of Sciences of the United States of America. 103 (19): 7246–51. Bibcode:2006PNAS..103.7246T. doi:10.1073/pnas.0600605103. PMC 1464328Freely accessible. PMID 16641091. Archived from the original on April 6, 2015. 
  35. ^ Farazdaghi, Hadi (2009). "Modeling the Kinetics of Activation and Reaction of Rubisco from Gas Exchange (12)". In Laisk A; Nedbal L; Govindjee. Photosynthesis in silico: Understanding Complexity from Molecules to Ecosystems. Advances in Photosynthesis and Respiration. 29. Berlin: Springer. ISBN 1-4020-9236-9. 
  36. ^ Bracher A, Whitney SM, Hartl FU, Hayer-Hartl M (April 2017). "Biogenesis and Metabolic Maintenance of Rubisco". Annual Review of Plant Biology. 68: 29–60. doi:10.1146/annurev-arplant-043015-111633. PMID 28125284. 
  37. ^ Sjuts I, Soll J, Bölter B (2017). "Import of Soluble Proteins into Chloroplasts and Potential Regulatory Mechanisms". Frontiers in Plant Science. 8: 168. doi:10.3389/fpls.2017.00168. PMID 28228773. 
  38. ^ Parry, M. A. J. (2003-05-01). "Manipulation of Rubisco: the amount, activity, function and regulation". Journal of Experimental Botany. 54 (386): 1321–1333. doi:10.1093/jxb/erg141. ISSN 0022-0957. 
  39. ^ Aigner H, Wilson RH, Bracher A, Calisse L, Bhat JY, Hartl FU, Hayer-Hartl M (December 2017). "E. coliwith five chloroplast chaperones including BSD2". Science. 358 (6368): 1272–1278. Bibcode:2017Sci...358.1272A. doi:10.1126/science.aap9221. PMID 29217567. 
  40. ^ a b Heazlewood, Joshua (2012). Proteomic applications in biology. New York: InTech Manhattan. ISBN 978-953-307-613-3. 
  41. ^ Gupta, Ravi; Kim, Sun Tae (2015). Proteomic Profiling. Methods in Molecular Biology. Humana Press, New York, NY. pp. 225–233. doi:10.1007/978-1-4939-2550-6_17. ISBN 9781493925490. 
  42. ^ Krishnan HB, Natarajan SS (December 2009). "A rapid method for depletion of Rubisco from soybean (Glycine max) leaf for proteomic analysis of lower abundance proteins". Phytochemistry. 70 (17–18): 1958–64. doi:10.1016/j.phytochem.2009.08.020. PMID 19766275. 
  43. ^ Kim, Sun Tae; Cho, Kyu Seong; Jang, Yu Sin; Kang, Kyu Young (2001-06-01). "Two-dimensional electrophoretic analysis of rice proteins by polyethylene glycol fractionation for protein arrays". ELECTROPHORESIS. 22 (10): 2103–2109. doi:10.1002/1522-2683(200106);2-w. ISSN 1522-2683. 
  44. ^ Xi J, Wang X, Li S, Zhou X, Yue L, Fan J, Hao D (November 2006). "Polyethylene glycol fractionation improved detection of low-abundant proteins by two-dimensional electrophoresis analysis of plant proteome". Phytochemistry. 67 (21): 2341–8. doi:10.1016/j.phytochem.2006.08.005. PMID 16973185. 
  45. ^ Cellar NA, Kuppannan K, Langhorst ML, Ni W, Xu P, Young SA (January 2008). "Cross species applicability of abundant protein depletion columns for ribulose-1,5-bisphosphate carboxylase/oxygenase". Journal of Chromatography. B, Analytical Technologies in the Biomedical and Life Sciences. 861 (1): 29–39. doi:10.1016/j.jchromb.2007.11.024. PMID 18063427. 
  46. ^ Agrawal GK, Jwa NS, Rakwal R (February 2009). "Rice proteomics: ending phase I and the beginning of phase II". Proteomics. 9 (4): 935–63. doi:10.1002/pmic.200800594. PMID 19212951. 
  47. ^ Cho, Jin-Hwan; Hwang, Heeyoun; Cho, Man-Ho; Kwon, Yong-Kook; Jeon, Jong-Seong; Bhoo, Seong Hee; Hahn, Tae-Ryong (2008-07-01). "The effect of DTT in protein preparations for proteomic analysis: Removal of a highly abundant plant enzyme, ribulose bisphosphate carboxylase/oxygenase". Journal of Plant Biology. 51 (4): 297–301. doi:10.1007/BF03036130. ISSN 1226-9239. 
  48. ^ Chase et al 1993.
  49. ^ Sage RF, Sage TL, Kocacinar F (2012). "Photorespiration and the evolution of C4 photosynthesis". Annual Review of Plant Biology. 63: 19–47. doi:10.1146/annurev-arplant-042811-105511. PMID 22404472. 
  50. ^ a b Studer RA, Christin PA, Williams MA, Orengo CA (February 2014). "Stability-activity tradeoffs constrain the adaptive evolution of RubisCO". Proceedings of the National Academy of Sciences of the United States of America. 111 (6): 2223–8. Bibcode:2014PNAS..111.2223S. doi:10.1073/pnas.1310811111. PMID 24469821. 
  51. ^ Wildman SG (2002). "Along the trail from Fraction I protein to Rubisco (ribulose bisphosphate carboxylase-oxygenase)". Photosynthesis Research. 73 (1–3): 243–50. doi:10.1023/A:1020467601966. PMID 16245127. 
    Portis AR, Parry MA (October 2007). "Discoveries in Rubisco (Ribulose 1,5-bisphosphate carboxylase/oxygenase): a historical perspective". Photosynthesis Research. 94 (1): 121–43. doi:10.1007/s11120-007-9225-6. PMID 17665149. 
Figure 3. In this figure, each protein chain in the (LS)2 complex is given its own color for easy identification.


External links

This page is based on a Wikipedia article. The text is available under the Creative Commons Attribution/Share-Alike License.

This tab holds the annotation information that is stored in the Pfam database. As we move to using Wikipedia as our main source of annotation, the contents of this tab will be gradually replaced by the Wikipedia tab.

Ribulose bisphosphate carboxylase large chain, catalytic domain Provide feedback

The C-terminal domain of RuBisCO large chain is the catalytic domain adopting a TIM barrel fold.

Literature references

  1. Taylor TC, Andersson I; , J Mol Biol 1997;265:432-444.: The structure of the complex between rubisco and its natural substrate ribulose 1,5-bisphosphate. PUBMED:9034362 EPMC:9034362

External database links

This tab holds annotation information from the InterPro database.

InterPro entry IPR000685

Ribulose bisphosphate carboxylase (RuBisCO) [PUBMED:6351728, PUBMED:12221984] catalyses the initial step in Calvin's reductive pentose phosphate cycle in plants as well as purple and green bacteria. It catalyzes the primary CO2 fixation step. RuBisCO consists of a large catalytic unit and a small subunit of undetermined function. In plants, the large subunit is coded by the chloroplastic genome while the small subunit is encoded in the nuclear genome. Rubisco is activated by carbamylation of an active site lysine, stabilized by a divalent cation, which then catalyzes the proton abstraction from the substrate ribulose 1,5 bisphosphate (RuBP) and leads to the formation of two molecules of 3-phosphoglycerate [PUBMED:1969412, PUBMED:9034362].

Gene Ontology

The mapping between Pfam and Gene Ontology is provided by InterPro. If you use this data please cite InterPro.

Domain organisation

Below is a listing of the unique domain organisations or architectures in which this domain is found. More...

Loading domain graphics...


We store a range of different sequence alignments for families. As well as the seed alignment from which the family is built, we provide the full alignment, generated by searching the sequence database (reference proteomes) using the family HMM. We also generate alignments using four representative proteomes (RP) sets, the UniProtKB sequence database, the NCBI sequence database, and our metagenomics sequence database. More...

View options

We make a range of alignments for each Pfam-A family. You can see a description of each above. You can view these alignments in various ways but please note that some types of alignment are never generated while others may not be available for all families, most commonly because the alignments are too large to handle.

Representative proteomes UniProt
Jalview View  View  View  View  View  View  View  View  View 
HTML View  View               
PP/heatmap 1 View               

1Cannot generate PP/Heatmap alignments for seeds; no PP data available

Key: ✓ available, x not generated, not available.

Format an alignment

Representative proteomes UniProt

Download options

We make all of our alignments available in Stockholm format. You can download them here as raw, plain text files or as gzip-compressed files.

Representative proteomes UniProt
Raw Stockholm Download   Download   Download   Download   Download   Download       Download  
Gzipped Download   Download   Download   Download   Download   Download       Download  

You can also download a FASTA format file containing the full-length sequences for all sequences in the full alignment.

HMM logo

HMM logos is one way of visualising profile HMMs. Logos provide a quick overview of the properties of an HMM in a graphical form. You can see a more detailed description of HMM logos and find out how you can interpret them here. More...


This page displays the phylogenetic tree for this family's seed alignment. We use FastTree to calculate neighbour join trees with a local bootstrap based on 100 resamples (shown next to the tree nodes). FastTree calculates approximately-maximum-likelihood phylogenetic trees from our seed alignment.

Note: You can also download the data file for the tree.

Curation and family details

This section shows the detailed information about the Pfam family. You can see the definitions of many of the terms in this section in the glossary and a fuller explanation of the scoring system that we use in the scores section of the help pages.

Curation View help on the curation process

Seed source: Prosite
Previous IDs: none
Type: Domain
Sequence Ontology: SO:0000417
Author: Sonnhammer ELL , Griffiths-Jones SR
Number in seed: 21
Number in full: 2433
Average length of the domain: 258.40 aa
Average identity of full alignment: 35 %
Average coverage of the sequence by the domain: 63.70 %

HMM information View help on HMM parameters

HMM build commands:
build method: hmmbuild -o /dev/null HMM SEED
search method: hmmsearch -Z 45638612 -E 1000 --cpu 4 HMM pfamseq
Model details:
Parameter Sequence Domain
Gathering cut-off 24.3 24.3
Trusted cut-off 24.9 24.3
Noise cut-off 23.9 24.2
Model length: 299
Family (HMM) version: 20
Download: download the raw HMM for this family

Species distribution

Sunburst controls


Weight segments by...

Change the size of the sunburst


Colour assignments

Archea Archea Eukaryota Eukaryota
Bacteria Bacteria Other sequences Other sequences
Viruses Viruses Unclassified Unclassified
Viroids Viroids Unclassified sequence Unclassified sequence


Align selected sequences to HMM

Generate a FASTA-format file

Clear selection

This visualisation provides a simple graphical representation of the distribution of this family across species. You can find the original interactive tree in the adjacent tab. More...

Loading sunburst data...

Tree controls


The tree shows the occurrence of this domain across different species. More...


Please note: for large trees this can take some time. While the tree is loading, you can safely switch away from this tab but if you browse away from the family page entirely, the tree will not be loaded.


There are 7 interactions for this family. More...

RuBisCO_large RcbX RuBisCO_large_N RcbX RuBisCO_small RuBisCO_large_N RuBisCO_small


For those sequences which have a structure in the Protein DataBank, we use the mapping between UniProt, PDB and Pfam coordinate systems from the PDBe group, to allow us to map Pfam domains onto UniProt sequences and three-dimensional protein structures. The table below shows the structures on which the RuBisCO_large domain has been found. There are 557 instances of this domain found in the PDB. Note that there may be multiple copies of the domain in a single PDB structure, since many structures contain multiple copies of the same protein sequence.

Loading structure mapping...