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50  structures 6023  species 0  interactions 17188  sequences 119  architectures

Family: PPDK_N (PF01326)

Summary: Pyruvate phosphate dikinase, AMP/ATP-binding 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 "Pyruvate, phosphate dikinase". More...

Pyruvate, phosphate dikinase Edit Wikipedia article

pyruvate, phosphate dikinase
EC no.
CAS no.9027-40-1
IntEnzIntEnz view
ExPASyNiceZyme view
MetaCycmetabolic pathway
PDB structuresRCSB PDB PDBe PDBsum
Gene OntologyAmiGO / QuickGO
Pyruvate, phosphate dikinase
Pyruvate phosphate dikinase dimer, Clostridium symbiosum (PDB: 1KC7​)
See domains below.
The three states of pyruvate, phosphate dikinase (unphosphorylated, monophosphorylated, and diphosphorylated) as it converts pyruvate to phosphoenolpyruvate (PEP). Pi = phosphate group. E-His = histidine residue of the enzyme.

Pyruvate, phosphate dikinase, or PPDK (EC is an enzyme in the family of transferases that catalyzes the chemical reaction

ATP + pyruvate + phosphate AMP + phosphoenolpyruvate + diphosphate

This enzyme has been studied primarily in plants, but it has been studied in some bacteria as well.[1] It is a key enzyme in gluconeogenesis and photosynthesis that is responsible for reversing the reaction performed by pyruvate kinase in Embden-Meyerhof-Parnas glycolysis. It should not be confused with pyruvate, water dikinase.

It belongs to the family of transferases, to be specific, those transferring phosphorus-containing groups (phosphotransferases) with paired acceptors (dikinases). This enzyme participates in pyruvate metabolism and carbon fixation.


The systematic name of this enzyme class is ATP:pyruvate, phosphate phosphotransferase. Other names in common use include pyruvate, orthophosphate dikinase, pyruvate-phosphate dikinase (phosphorylating), pyruvate phosphate dikinase, pyruvate-inorganic phosphate dikinase, pyruvate-phosphate dikinase, pyruvate-phosphate ligase, pyruvic-phosphate dikinase, pyruvic-phosphate ligase, pyruvate, Pi dikinase, and PPDK.

Reaction mechanism

PPDK catalyses the conversion of pyruvate to phosphoenolpyruvate (PEP), consuming 1 molecule of ATP, and producing one molecule of AMP in the process. The mechanism consists of 3 reversible reactions:[2]

  1. The enzyme PPDK binds to ATP, to produce AMP and a diphosphorylated PPDK.
  2. The diphosphorylated PPDK binds to inorganic phosphate, producing diphosphate and (mono)phosphorylated PPDK.
  3. Phosphorylated PPDK binds to pyruvate, producing phosphoenolpyruvate, and regenerating PPDK.

The reaction is similar to the reaction catalysed by pyruvate kinase, which also converts pyruvate to PEP.[3] However, pyruvate kinase catalyses an irreversible reaction, and does not consume ATP. By contrast, PPDK catalyses a reversible reaction, and consumes 1 molecule of ATP for each molecule of pyruvate converted.

Currently, the details of each mechanistic step is unknown[3]


In its active form, PPDK is a homotetramer with subunits about 95 kDa[4]

There are two different reaction centres about 45 Angstroms apart, in which different substrates bind.[5] The nucleotide (ATP) binding site is on the N-terminus, has 240 amino acids, and a characteristic ATP-grasp. The pyruvate/PEP binding site is on the C-terminus, has 340 amino acids, and an α/β-barrel fold. There is also a central domain, which contains His455, the primary residue responsible for catalysis. His455 is the phosphoryl acceptor or donor residue.[3] The structure of the enzyme suggests that the His455 arm undergoes a swivelling motion to shuttle a phosphoryl group between the two reaction centres.[6] During this swivelling, the central domain rotates at least 92 degrees, and translates 0.5 Angstroms.[7]

Studies of crystal structures of PPDK show that the central domain is located in different proximity to the two other domains depending on the source of the enzyme.[7] In maize, it is closer to the C-terminal, while in Clostridium symbiosum, it is closer to the N-terminal.

Research has shown that the PPDK binding mechanisms are similar to that of D-Ala-D-Ala ligase and pyruvate kinase.[5] In particular, PPDK is very similar to pyruvate kinase, which also catalyses the conversion of pyruvate to phosphoenolpyruvate; however, it does so without a phosphorylated-enzyme intermediate.[3] Though their amino acid sequences are different, residues key to catalysis are preserved in both enzymes. Point-mutagenesis experiments have shown that catalytic residues include Arg561, Arg617, Glu745, Asn768, and Cys831 (numbering relative to the C, symbiosum protein, PDB: 1KBL, 1KC7​).[3]

Protein domain infoboxes
Pyruvate phosphate dikinase, N-teminal ATP-grasp
SCOP2d1vbga3 / SCOPe / SUPFAM
CATH domains 1vbgA01-1vbgA04
PEP-utilizing enzyme, Central motile domain
SCOP2d1vbga2 / SCOPe / SUPFAM
PEP-utilizing enzyme, C-terminal PEP-binding
SCOP2d1vbga1 / SCOPe / SUPFAM

Biological function and evolution

PPDK is used in the C4 pathway, to improve the efficiency of carbon dioxide fixation.[8] In environments where there is a lot of light, the rate of photosynthesis in plants is limited by the rate of carbon dioxide (CO2) uptake. This can be improved by using a series of chemical reactions to transport CO2 from mesophyll cells (which are located on the outside of a leaf) to bundle sheath cells (which are located inside the cells). PPDK converts pyruvate to PEP, which reacts with CO2 to produce oxaloacetate. When CO2 is released in the bundle sheath cells, pyruvate is regenerated, and the cycle continues.[8]

Though the reaction catalysed by PPDK is reversible, PEP is favoured as the product in biological conditions. This is due to the basic pH in the stroma, where the reaction occurs, as well as high concentrations of adenylate kinase and pyrophosphatase. Because these two enzymes catalyse exergonic reactions involving AMP, and disphosphate, respectively, they drive the PPDK-catalysed reaction forward.[9] Because PPDK consumes ATP, the C4 pathway is unfavourable for plants in environments with little access to light, as they are unable to produce large quantities of ATP.[8]

PPDK is highly abundant in C4 leaves, comprising up to 10% of total protein.[10] Research has shown that the enzyme is about 96% identical in different species of plants. Hybridization experiments revealed that the genetic differences correlate with the extent to which the plants perform the C4 pathway – the uncommon sequences exist in plants which also display C3 characteristics.[11] PPDK is also found in small quantities in C3 plants. Evolutionary history suggests that it once had a role in glycolysis like the similar pyruvate kinase, and eventually evolved into the C4 pathway.[10]

Besides plants, PPDK is also found in the parasitic ameoba Entamoeba histolytica (P37213) and the bacteria Clostridium symbiosum (P22983; as well as other bacteria).[12] In those two organisms PPDK functions similarly to (and sometimes in place of) pyruvate kinase, catalyzing the reaction in the ATP-producing direction as a part of glycolysis. Inhibitors for the Entamoeba PPDK have been proposed as amebicides against this organism.[13]


PPDK is inactivated when PPDK Regulatory Protein (PDRP) phosphorylates Thr456. PDRP both activates and inactivates PPDK.

Plant PPDK is regulated by the pyruvate, phosphate dikinase regulatory protein (PDRP).[4] When levels of light are high, PDRP dephosphorylates Thr456 on PPDK using AMP, thus activating the enzyme.[10] PDRP deactivates PPDK by phosphorylating the same threonine residue, using diphosphate. PDRP is a unique regulator because it catalyses both activation and deactivation of PPDK, through two different mechanisms.[10]

Research on maize PPDK suggests that introns, terminator sequences, and perhaps other enhancer sequences, act cooperatively to increase the level of functional and stable mRNA. PPDK cDNA was expressed only slightly in transgenic rice, compared to intact DNA which saw significant expression.[14]

Structural studies

As of early 2018, 14 structures have been solved for this class of enzymes, with PDB accession codes 1DIK, 1GGO, 1H6Z, 1JDE, 1KBL, 1KC7, 1VBG, 1VBH, 2DIK, 2FM4, 5JVJ, 5JVL, 5JVN, 5LU4.


  1. ^ Pocalyko DJ, Carroll LJ, Martin BM, Babbitt PC, Dunaway-Mariano D (December 1990). "Analysis of sequence homologies in plant and bacterial pyruvate phosphate dikinase, enzyme I of the bacterial phosphoenolpyruvate: sugar phosphotransferase system and other PEP-utilizing enzymes. Identification of potential catalytic and regulatory motifs". Biochemistry. 29 (48): 10757–65. doi:10.1021/bi00500a006. PMID 2176881.
  2. ^ Evans HJ, Wood HG (December 1968). "The mechanism of the pyruvate, phosphate dikinase reaction". Proceedings of the National Academy of Sciences of the United States of America. 61 (4): 1448–53. Bibcode:1968PNAS...61.1448E. doi:10.1073/pnas.61.4.1448. PMC 225276. PMID 4303480.
  3. ^ a b c d e Herzberg O, Chen CC, Liu S, Tempczyk A, Howard A, Wei M, et al. (January 2002). "Pyruvate site of pyruvate phosphate dikinase: crystal structure of the enzyme-phosphonopyruvate complex, and mutant analysis". Biochemistry. 41 (3): 780–7. doi:10.1021/bi011799+. PMID 11790099.
  4. ^ a b Chastain CJ, Failing CJ, Manandhar L, Zimmerman MA, Lakner MM, Nguyen TH (May 2011). "Functional evolution of C(4) pyruvate, orthophosphate dikinase". Journal of Experimental Botany. 62 (9): 3083–91. doi:10.1093/jxb/err058. PMID 21414960.
  5. ^ a b Herzberg O, Chen CC, Kapadia G, McGuire M, Carroll LJ, Noh SJ, Dunaway-Mariano D (April 1996). "Swiveling-domain mechanism for enzymatic phosphotransfer between remote reaction sites". Proceedings of the National Academy of Sciences of the United States of America. 93 (7): 2652–7. Bibcode:1996PNAS...93.2652H. doi:10.1073/pnas.93.7.2652. PMC 39685. PMID 8610096.
  6. ^ Lim K, Read RJ, Chen CC, Tempczyk A, Wei M, Ye D, et al. (December 2007). "Swiveling domain mechanism in pyruvate phosphate dikinase". Biochemistry. 46 (51): 14845–53. CiteSeerX doi:10.1021/bi701848w. PMID 18052212.
  7. ^ a b Nakanishi T, Nakatsu T, Matsuoka M, Sakata K, Kato H (February 2005). "Crystal structures of pyruvate phosphate dikinase from maize revealed an alternative conformation in the swiveling-domain motion". Biochemistry. 44 (4): 1136–44. doi:10.1021/bi0484522. PMID 15667207.
  8. ^ a b c Berg J, Tymoczko J, Stryer L (2012). "The Calvin Cycle and the Pentose Phosphate Pathway". Biochemistry (7th ed.). New York: W.H Freeman. pp. 599–600. ISBN 9780716787242.
  9. ^ Chastain C (2010). "Structure, Function, and Post-Translational Regulation of C4 Pyruvate Orthophosphate Dikinase". In Raghavendra A (ed.). C4 Photosynthesis and Related CO2 Concentrating Mechanisms. pp. 301–305. ISBN 9789048194063.
  10. ^ a b c d Chastain CJ, Fries JP, Vogel JA, Randklev CL, Vossen AP, Dittmer SK, et al. (April 2002). "Pyruvate,orthophosphate dikinase in leaves and chloroplasts of C(3) plants undergoes light-/dark-induced reversible phosphorylation". Plant Physiology. 128 (4): 1368–78. doi:10.1104/pp.010806. PMC 154264. PMID 11950985.
  11. ^ Rosche E, Streubel M, Westhoff P (October 1994). "Primary structure of the photosynthetic pyruvate orthophosphate dikinase of the C3 plant Flaveria pringlei and expression analysis of pyruvate orthophosphate dikinase sequences in C3, C3-C4 and C4 Flaveria species". Plant Molecular Biology. 26 (2): 763–9. doi:10.1007/bf00013761. PMID 7948930. S2CID 23276817.
  12. ^ UniProt 50%-90% clusters: From Clostridium PPDK
  13. ^ Stephen P, Vijayan R, Bhat A, Subbarao N, Bamezai RN (September 2008). "Molecular modeling on pyruvate phosphate dikinase of Entamoeba histolytica and in silico virtual screening for novel inhibitors". Journal of Computer-Aided Molecular Design. 22 (9): 647–60. Bibcode:2008JCAMD..22..647S. doi:10.1007/s10822-007-9130-2. PMID 17710553. S2CID 25026913.
  14. ^ Fukayama H, Tsuchida H, Agarie S, Nomura M, Onodera H, Ono K, et al. (November 2001). "Significant accumulation of C(4)-specific pyruvate, orthophosphate dikinase in a C(3) plant, rice". Plant Physiology. 127 (3): 1136–46. doi:10.1104/pp.010641. PMC 129282. PMID 11706193.

Further reading

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.

Pyruvate phosphate dikinase, AMP/ATP-binding domain Provide feedback

This enzyme catalyses the reversible conversion of ATP to AMP, pyrophosphate and phosphoenolpyruvate (PEP). The N-terminal domain has been shown to be the AMP/ATP-binding domain [1].

Literature references

  1. Lim K, Read RJ, Chen CC, Tempczyk A, Wei M, Ye D, Wu C, Dunaway-Mariano D, Herzberg O;, Biochemistry. 2007;46:14845-14853.: Swiveling domain mechanism in pyruvate phosphate dikinase. PUBMED:18052212 EPMC:18052212

External database links

This tab holds annotation information from the InterPro database.

InterPro entry IPR002192

This enzyme catalyses the reversible conversion of ATP to AMP, pyrophosphate and phosphoenolpyruvate (PEP) [ PUBMED:8610096 ]. This domain is present at the N terminus of some PEP-utilizing enzymes, and has been shown to be the AMP/ATP-binding domain [ PUBMED:18052212 ].

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...

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Pfam Clan

This family is a member of clan ATP-grasp (CL0179), which has the following description:

The ATP-grasp domain is found in a wide variety of carboxylate-amine/thiol ligases [1]. It is composed of two subdomains, with ATP being bound in the cleft between the two.

The clan contains the following 26 members:

ATP-grasp ATP-grasp_2 ATP-grasp_3 ATP-grasp_4 ATP-grasp_5 ATP-grasp_6 ATPgrasp_ST ATPgrasp_Ter ATPgrasp_TupA ATPgrasp_YheCD CP_ATPgrasp_1 CP_ATPgrasp_2 CPSase_L_D2 D123 Dala_Dala_lig_C DUF1297 GARS_A GSH-S_ATP GSP_synth Ins134_P3_kin PPDK_N R2K_2 R2K_3 RimK Synapsin_C TTL


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 and the UniProtKB sequence database. More...

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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: Sarah Teichmann
Previous IDs: PPDK_N_term;
Type: Family
Sequence Ontology: SO:0100021
Author: Finn RD , Bateman A
Number in seed: 103
Number in full: 17188
Average length of the domain: 221.20 aa
Average identity of full alignment: 23 %
Average coverage of the sequence by the domain: 37.19 %

HMM information View help on HMM parameters

HMM build commands:
build method: hmmbuild -o /dev/null HMM SEED
search method: hmmsearch -Z 61295632 -E 1000 --cpu 4 HMM pfamseq
Model details:
Parameter Sequence Domain
Gathering cut-off 27.0 27.0
Trusted cut-off 27.0 27.0
Noise cut-off 26.9 26.9
Model length: 328
Family (HMM) version: 22
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Species distribution

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Archea Archea Eukaryota Eukaryota
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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 PPDK_N domain has been found. There are 50 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.

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AlphaFold Structure Predictions

The list of proteins below match this family and have AlphaFold predicted structures. Click on the protein accession to view the predicted structure.

Protein Predicted structure External Information
A0A0P0WWR8 View 3D Structure Click here
A0A0R0ESA5 View 3D Structure Click here
A0A0R0I7Q2 View 3D Structure Click here
A0A0R0J8M3 View 3D Structure Click here
A0A1D6IVK7 View 3D Structure Click here
A0A1D6LTL9 View 3D Structure Click here
A0A1D6M411 View 3D Structure Click here
A4HV09 View 3D Structure Click here
I1KXC2 View 3D Structure Click here
K7MJI6 View 3D Structure Click here
K7MS29 View 3D Structure Click here
O06579 View 3D Structure Click here
O23404 View 3D Structure Click here
O27190 View 3D Structure Click here
O29548 View 3D Structure Click here
O34309 View 3D Structure Click here
O34796 View 3D Structure Click here
O67899 View 3D Structure Click here
O83026 View 3D Structure Click here
P11155 View 3D Structure Click here
P23538 View 3D Structure Click here
P42850 View 3D Structure Click here
P46893 View 3D Structure Click here
P56070 View 3D Structure Click here
Q0DC10 View 3D Structure Click here
Q1RH78 View 3D Structure Click here
Q22649 View 3D Structure Click here
Q2QTC2 View 3D Structure Click here
Q42368 View 3D Structure Click here
Q4E0Q0 View 3D Structure Click here
Q4E3P5 View 3D Structure Click here
Q55905 View 3D Structure Click here
Q57962 View 3D Structure Click here
Q59754 View 3D Structure Click here
Q6AVA8 View 3D Structure Click here
Q6ZY51 View 3D Structure Click here
Q75KR1 View 3D Structure Click here
Q9AWA5 View 3D Structure Click here
Q9K0I2 View 3D Structure Click here
Q9SAC6 View 3D Structure Click here