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.
46  structures 7887  species 5  interactions 9491  sequences 98  architectures

Family: CPSase_L_D3 (PF02787)

Summary: Carbamoyl-phosphate synthetase large chain, oligomerisation 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 "Carbamoyl phosphate synthetase". More...

Carbamoyl phosphate synthetase Edit Wikipedia article

CPSase large subunit ATP-binding domain
PDB 1dv2 EBI.jpg
the structure of biotin carboxylase, mutant e288k, complexed with atp
Identifiers
Symbol CPSase_L_D2
Pfam PF02786
Pfam clan CL0179
InterPro IPR005479
PROSITE PDOC00676
SCOP 1bnc
SUPERFAMILY 1bnc
CPSase large subunit oligomerisation domain
PDB 1bxr EBI.jpg
structure of carbamoyl phosphate synthetase complexed with the atp analog amppnp
Identifiers
Symbol CPSase_L_D3
Pfam PF02787
InterPro IPR005480
PROSITE PDOC00676
SCOP 1bnc
SUPERFAMILY 1bnc
CPSase large subunit N-terminal domain
PDB 1ulz EBI.jpg
crystal structure of the biotin carboxylase subunit of pyruvate carboxylase
Identifiers
Symbol CPSase_L_chain
Pfam PF00289
InterPro IPR005481
PROSITE PDOC00676
SCOP 1bnc
SUPERFAMILY 1bnc
CPSase small subunit N-terminal domain
PDB 1kee EBI.jpg
inactivation of the amidotransferase activity of carbamoyl phosphate synthetase by the antibiotic acivicin
Identifiers
Symbol CPSase_sm_chain
Pfam PF00988
InterPro IPR002474
PROSITE PDOC00676
SCOP 1jdb
SUPERFAMILY 1jdb

Carbamoyl phosphate synthetase catalyzes the ATP-dependent synthesis of carbamoyl phosphate from glutamine (EC 6.3.5.5) or ammonia (EC 6.3.4.16) and bicarbonate.[1] This enzyme catalyzes the reaction of ATP and bicarbonate to produce carboxy phosphate and ADP. Carboxy phosphate reacts with ammonia to give carbamic acid. In turn, carbamic acid reacts with a second ATP to give carbamoyl phosphate plus ADP.

It represents the first committed step in pyrimidine and arginine biosynthesis in prokaryotes and eukaryotes, and in the urea cycle in most terrestrial vertebrates.[2] Most prokaryotes carry one form of CPSase that participates in both arginine and pyrimidine biosynthesis, however certain bacteria can have separate forms.

There are three different forms that serve very different functions:

Mechanism

Carbamoyl phosphate synthase has three main steps in its mechanism and is, in essence, irreversible.[4]

  1. Bicarbonate ion is phosphorylated with ATP to create carboxylphosphate.
  2. The carboxylphosphate then reacts with ammonia to form carbamic acid, releasing inorganic phosphate.
  3. A second molecule of ATP then phosphorylates carbamic acid, creating carbamoyl phosphate.

The activity of the enzyme is known to be inhibited by both Tris and HEPES buffers.[5]

Structure

Carbamoyl phosphate synthase (CPSase) is a heterodimeric enzyme composed of a small and a large subunit (with the exception of CPSase III, which is composed of a single polypeptide that may have arisen from gene fusion of the glutaminase and synthetase domains).[2][3][6] CPSase has three active sites, one in the small subunit and two in the large subunit. The small subunit contains the glutamine binding site and catalyses the hydrolysis of glutamine to glutamate and ammonia, which is in turn used by the large chain to synthesize carbamoyl phosphate. The small subunit has a 3-layer beta/beta/alpha structure, and is thought to be mobile in most proteins that carry it. The C-terminal domain of the small subunit of CPSase has glutamine amidotransferase activity. The large subunit has two homologous carboxy phosphate domains, both of which have ATP-binding sites; however, the N-terminal carboxy phosphate domain catalyses the phosphorylation of biocarbonate, while the C-terminal domain catalyses the phosphorylation of the carbamate intermediate.[7] The carboxy phosphate domain found duplicated in the large subunit of CPSase is also present as a single copy in the biotin-dependent enzymes acetyl-CoA carboxylase (ACC), propionyl-CoA carboxylase (PCCase), pyruvate carboxylase (PC) and urea carboxylase.

The large subunit in bacterial CPSase has four structural domains: the carboxy phosphate domain 1, the oligomerisation domain, the carbamoyl phosphate domain 2 and the allosteric domain.[8] CPSase heterodimers from Escherichia coli contain two molecular tunnels: an ammonia tunnel and a carbamate tunnel. These inter-domain tunnels connect the three distinct active sites, and function as conduits for the transport of unstable reaction intermediates (ammonia and carbamate) between successive active sites.[9] The catalytic mechanism of CPSase involves the diffusion of carbamate through the interior of the enzyme from the site of synthesis within the N-terminal domain of the large subunit to the site of phosphorylation within the C-terminal domain.

References

  1. ^ Simmer JP, Kelly RE, Scully JL, Evans DR, Rinker Jr AG (1990). "Mammalian carbamyl phosphate synthetase (CPS). DNA sequence and evolution of the CPS domain of the Syrian hamster multifunctional protein CAD". J. Biol. Chem. 265 (18): 10395–10402. PMID 1972379. 
  2. ^ a b Holden HM, Thoden JB, Raushel FM (October 1999). "Carbamoyl phosphate synthetase: an amazing biochemical odyssey from substrate to product". Cell. Mol. Life Sci. 56 (5–6): 507–22. doi:10.1007/s000180050448. PMID 11212301. 
  3. ^ a b Saha N, Datta S, Kharbuli ZY, Biswas K, Bhattacharjee A (July 2007). "Air-breathing catfish, Clarias batrachus upregulates glutamine synthetase and carbamyl phosphate synthetase III during exposure to high external ammonia". Comp. Biochem. Physiol. B, Biochem. Mol. Biol. 147 (3): 520–30. doi:10.1016/j.cbpb.2007.03.007. PMID 17451989. 
  4. ^ Biochemistry, 3rd edition, J.M. Berg, J.L. Tymoczko, L. Stryer
  5. ^ Lund, P.; Wiggins, D. (1987). "Inhibition of carbamoyl-phosphate synthase (ammonia) by Tris and Hepes. Effect on Ka for N-acetylglutamate" (PDF). Biochem. J. 243 (1): 273–276. PMC 1147843Freely accessible. PMID 3606575. 
  6. ^ Raushel FM, Thoden JB, Holden HM (June 1999). "The amidotransferase family of enzymes: molecular machines for the production and delivery of ammonia". Biochemistry. 38 (25): 7891–9. doi:10.1021/bi990871p. PMID 10387030. 
  7. ^ Stapleton MA, Javid-Majd F, Harmon MF, Hanks BA, Grahmann JL, Mullins LS, Raushel FM (November 1996). "Role of conserved residues within the carboxy phosphate domain of carbamoyl phosphate synthetase". Biochemistry. 35 (45): 14352–61. doi:10.1021/bi961183y. PMID 8916922. 
  8. ^ Thoden JB, Raushel FM, Benning MM, Rayment I, Holden HM (January 1999). "The structure of carbamoyl phosphate synthetase determined to 2.1 A resolution". Acta Crystallogr. D. 55 (Pt 1): 8–24. doi:10.1107/S0907444998006234. PMID 10089390. 
  9. ^ Kim J, Howell S, Huang X, Raushel FM (October 2002). "Structural defects within the carbamate tunnel of carbamoyl phosphate synthetase". Biochemistry. 41 (42): 12575–81. doi:10.1021/bi020421o. PMID 12379099. 

External links

This article incorporates text from the public domain Pfam and InterPro IPR005479

This article incorporates text from the public domain Pfam and InterPro IPR005480

This article incorporates text from the public domain Pfam and InterPro IPR005481

This article incorporates text from the public domain Pfam and InterPro IPR002474

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.

Carbamoyl-phosphate synthetase large chain, oligomerisation domain Provide feedback

Carbamoyl-phosphate synthase catalyses the ATP-dependent synthesis of carbamyl-phosphate from glutamine or ammonia and bicarbonate. The carbamoyl-phosphate synthase (CPS) enzyme in prokaryotes is a heterodimer of a small and large chain.

Literature references

  1. Thoden JB, Raushel FM, Benning MM, Rayment I, Holden HM; , Acta Crystallogr D Biol Crystallogr 1999;55:8-24.: The structure of carbamoyl phosphate synthetase determined to 2.1 A resolution. PUBMED:10089390 EPMC:10089390


External database links

This tab holds annotation information from the InterPro database.

InterPro entry IPR005480

This entry represents the oligomerisation domain found in the large subunit of carbamoyl phosphate synthases as well as in certain other carboxy phosphate domain-containing enzymes. This domain forms a primarily alpha-helical fold [PUBMED:10089390].

Domain organisation

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

Loading domain graphics...

Pfam Clan

This family is a member of clan HTH (CL0123), which has the following description:

This family contains a diverse range of mostly DNA-binding domains that contain a helix-turn-helix motif.

The clan contains the following 340 members:

AbiEi_3_N AbiEi_4 ANAPC2 AphA_like Arg_repressor ARID ArsR B-block_TFIIIC B5 Bac_DnaA_C Baculo_PEP_N BetR BHD_3 BLACT_WH Bot1p BrkDBD BsuBI_PstI_RE_N C_LFY_FLO CaiF_GrlA CarD_CdnL_TRCF CDC27 Cdc6_C Cdh1_DBD_1 CDT1 CDT1_C CENP-B_N Costars CPSase_L_D3 Cro Crp CSN4_RPN5_eIF3a CSN8_PSD8_EIF3K CtsR Cullin_Nedd8 CUT CUTL CvfB_WH DBD_HTH DDRGK DEP Dimerisation Dimerisation2 DNA_meth_N DpnI_C DprA_WH DsrC DsrD DUF1016_N DUF1133 DUF1153 DUF1323 DUF134 DUF1441 DUF1492 DUF1495 DUF1670 DUF1804 DUF1819 DUF1836 DUF1870 DUF2089 DUF2250 DUF2316 DUF2513 DUF2582 DUF3116 DUF3253 DUF3853 DUF3860 DUF3908 DUF433 DUF4364 DUF4423 DUF4447 DUF480 DUF4817 DUF5635 DUF573 DUF722 DUF739 DUF742 DUF977 E2F_TDP EAP30 eIF-5_eIF-2B ELL ESCRT-II Ets EutK_C Exc F-112 FaeA Fe_dep_repr_C Fe_dep_repress FeoC FokI_C FokI_N Forkhead FtsK_gamma FUR GcrA GerE GntR GP3_package HARE-HTH HemN_C HNF-1_N Homeobox_KN Homeodomain Homez HPD HrcA_DNA-bdg HSF_DNA-bind HTH_1 HTH_10 HTH_11 HTH_12 HTH_13 HTH_15 HTH_16 HTH_17 HTH_18 HTH_19 HTH_20 HTH_21 HTH_22 HTH_23 HTH_24 HTH_25 HTH_26 HTH_27 HTH_28 HTH_29 HTH_3 HTH_30 HTH_31 HTH_32 HTH_33 HTH_34 HTH_35 HTH_36 HTH_37 HTH_38 HTH_39 HTH_40 HTH_41 HTH_42 HTH_43 HTH_45 HTH_46 HTH_47 HTH_48 HTH_49 HTH_5 HTH_50 HTH_51 HTH_52 HTH_53 HTH_54 HTH_55 HTH_56 HTH_57 HTH_6 HTH_7 HTH_8 HTH_9 HTH_ABP1_N HTH_AraC HTH_AsnC-type HTH_CodY HTH_Crp_2 HTH_DeoR HTH_IclR HTH_Mga HTH_micro HTH_OrfB_IS605 HTH_ParB HTH_psq HTH_Tnp_1 HTH_Tnp_1_2 HTH_Tnp_4 HTH_Tnp_IS1 HTH_Tnp_IS630 HTH_Tnp_ISL3 HTH_Tnp_Mu_1 HTH_Tnp_Mu_2 HTH_Tnp_Tc3_1 HTH_Tnp_Tc3_2 HTH_Tnp_Tc5 HTH_WhiA HxlR IBD IF2_N IRF KicB KilA-N Kin17_mid KORA KorB La LacI LexA_DNA_bind Linker_histone LZ_Tnp_IS481 MADF_DNA_bdg MAGE MarR MarR_2 MerR MerR-DNA-bind MerR_1 MerR_2 Mga Mnd1 MogR_DNAbind Mor MotA_activ MqsA_antitoxin MRP-L20 MukE Myb_DNA-bind_2 Myb_DNA-bind_3 Myb_DNA-bind_4 Myb_DNA-bind_5 Myb_DNA-bind_6 Myb_DNA-bind_7 Myb_DNA-binding Neugrin NFRKB_winged NOD2_WH NUMOD1 ORC_WH_C OST-HTH P22_Cro PaaX PadR PapB PAX PCI Penicillinase_R Phage_AlpA Phage_antitermQ Phage_CI_repr Phage_CII Phage_NinH Phage_Nu1 Phage_rep_O Phage_rep_org_N Phage_terminase PheRS_DBD1 PheRS_DBD2 PheRS_DBD3 Pou Pox_D5 PqqD PRC2_HTH_1 PUFD PuR_N Put_DNA-bind_N Raf1_HTH Rap1-DNA-bind Rep_3 RepA_C RepA_N RepC RepL Replic_Relax RFX_DNA_binding Ribosomal_S18 Ribosomal_S19e Ribosomal_S25 Rio2_N RNA_pol_Rpc34 RNA_pol_Rpc82 RNase_H2-Ydr279 ROQ_II RP-C RPA RPA_C RQC Rrf2 RTP RuvB_C S10_plectin SAC3_GANP SANT_DAMP1_like SatD SelB-wing_1 SelB-wing_2 SelB-wing_3 SgrR_N Sigma54_CBD Sigma54_DBD Sigma70_ECF Sigma70_ner Sigma70_r2 Sigma70_r3 Sigma70_r4 Sigma70_r4_2 Ski_Sno SLIDE Slx4 SMC_Nse1 SMC_ScpB SoPB_HTH SpoIIID SRP19 SRP_SPB STN1_2 Sulfolobus_pRN Sun2_CC2 Suv3_N Swi6_N SWIRM Tau95 TBPIP TEA Terminase_5 TetR_N TFA2_Winged_2 TFIIE_alpha TFIIE_beta TFIIF_alpha TFIIF_beta Tn7_Tnp_TnsA_C Tn916-Xis TraI_2_C Trans_reg_C TrfA TrmB tRNA_bind_2 tRNA_bind_3 Trp_repressor UPF0122 UPF0175 Vir_act_alpha_C YdaS_antitoxin YjcQ YokU z-alpha

Alignments

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.

  Seed
(1084)
Full
(9491)
Representative proteomes UniProt
(36536)
NCBI
(45908)
Meta
(2577)
RP15
(2301)
RP35
(5954)
RP55
(8991)
RP75
(12624)
Jalview View  View  View  View  View  View  View  View  View 
HTML View                 
PP/heatmap 1                

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

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

Format an alignment

  Seed
(1084)
Full
(9491)
Representative proteomes UniProt
(36536)
NCBI
(45908)
Meta
(2577)
RP15
(2301)
RP35
(5954)
RP55
(8991)
RP75
(12624)
Alignment:
Format:
Order:
Sequence:
Gaps:
Download/view:

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.

  Seed
(1084)
Full
(9491)
Representative proteomes UniProt
(36536)
NCBI
(45908)
Meta
(2577)
RP15
(2301)
RP35
(5954)
RP55
(8991)
RP75
(12624)
Raw Stockholm Download   Download   Download   Download   Download   Download   Download   Download   Download  
Gzipped Download   Download   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...

Trees

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: ref [1]
Previous IDs: none
Type: Domain
Sequence Ontology: SO:0000417
Author: Griffiths-Jones SR
Number in seed: 1084
Number in full: 9491
Average length of the domain: 121.70 aa
Average identity of full alignment: 38 %
Average coverage of the sequence by the domain: 10.41 %

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 26.6 26.6
Trusted cut-off 26.6 28.3
Noise cut-off 26.5 26.4
Model length: 122
Family (HMM) version: 19
Download: download the raw HMM for this family

Species distribution

Sunburst controls

Hide

Weight segments by...


Change the size of the sunburst

Small
Large

Colour assignments

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

Selections

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

Hide

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

Loading...

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.

Interactions

There are 5 interactions for this family. More...

GATase CPSase_sm_chain CPSase_L_D3 CPSase_L_D2 Biotin_carb_N

Structures

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 CPSase_L_D3 domain has been found. There are 46 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...