Summary: Carbamoyl-phosphate synthase L chain, ATP binding domain
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Carbamoyl-phosphate synthase L chain, ATP binding domain Provide feedback
Carbamoyl-phosphate synthase catalyses the ATP-dependent synthesis of carbamyl-phosphate from glutamine or ammonia and bicarbonate. This important enzyme initiates both the urea cycle and the biosynthesis of arginine and/or pyrimidines . The carbamoyl-phosphate synthase (CPS) enzyme in prokaryotes is a heterodimer of a small and large chain. The small chain promotes the hydrolysis of glutamine to ammonia, which is used by the large chain to synthesise carbamoyl phosphate. See PF00988. The small chain has a GATase domain in the carboxyl terminus. See PF00117. The ATP binding domain (this one) has an ATP-grasp fold.
Simmer JP, Kelly RE, Rinker AG Jr, Scully JL, Evans DR; , Biol Chem 1990;265:10395-10402.: Mammalian carbamyl phosphate synthetase (CPS). DNA sequence and evolution of the CPS domain of the Syrian hamster multifunctional protein CAD. PUBMED:1972379 EPMC:1972379
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 IPR005479
Carbamoyl phosphate synthase (CPSase) is a heterodimeric enzyme composed of a small and a large subunit (with the exception of CPSase III, see below). CPSase catalyses the synthesis of carbamoyl phosphate from biocarbonate, ATP and glutamine (EC) or ammonia (EC), and represents the first committed step in pyrimidine and arginine biosynthesis in prokaryotes and eukaryotes, and in the urea cycle in most terrestrial vertebrates [PUBMED:10387030, PUBMED:11212301]. 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. 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 [PUBMED:8916922]. 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 (EC) (ACC), propionyl-CoA carboxylase (EC) (PCCase), pyruvate carboxylase (EC) (PC) and urea carboxylase (EC).
Most prokaryotes carry one form of CPSase that participates in both arginine and pyrimidine biosynthesis, however certain bacteria can have separate forms. 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 [PUBMED:10089390]. 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 [PUBMED:12379099]. 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.
Eukaryotes have two distinct forms of CPSase: a mitochondrial enzyme (CPSase I) that participates in both arginine biosynthesis and the urea cycle; and a cytosolic enzyme (CPSase II) involved in pyrimidine biosynthesis. CPSase II occurs as part of a multi-enzyme complex along with aspartate transcarbamoylase and dihydroorotase; this complex is referred to as the CAD protein [PUBMED:7907330]. The hepatic expression of CPSase is transcriptionally regulated by glucocorticoids and/or cAMP [PUBMED:17397987]. There is a third form of the enzyme, CPSase III, found in fish, which uses glutamine as a nitrogen source instead of ammonia [PUBMED:17451989]. CPSase III is closely related to CPSase I, and is composed of a single polypeptide that may have arisen from gene fusion of the glutaminase and synthetase domains [PUBMED:7932737].
This entry represents the ATP-binding domain found in the large subunit of carbamoyl phosphate synthase, as well as in other proteins, including acetyl-CoA carboxylases and pyruvate carboxylases.
The mapping between Pfam and Gene Ontology is provided by InterPro. If you use this data please cite InterPro.
|Molecular function||ATP binding (GO:0005524)|
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The ATP-grasp domain is found in a wide variety of carboxylate-amine/thiol ligases . It is composed of two subdomains, with ATP being bound in the cleft between the two.
The clan contains the following 21 members:ATP-grasp ATP-grasp_2 ATP-grasp_3 ATP-grasp_4 ATP-grasp_5 ATPgrasp_ST ATPgrasp_Ter ATPgrasp_TupA ATPgrasp_YheCD CP_ATPgrasp_1 CP_ATPgrasp_2 CPSase_L_D2 Dala_Dala_lig_C DUF1297 GARS_A GSH-S_ATP GSP_synth Ins134_P3_kin RimK Synapsin_C TTL
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|Author:||Finn RD, Griffiths-Jones SR|
|Number in seed:||16|
|Number in full:||9834|
|Average length of the domain:||202.50 aa|
|Average identity of full alignment:||31 %|
|Average coverage of the sequence by the domain:||26.66 %|
|HMM build commands:||
build method: hmmbuild -o /dev/null HMM SEED
search method: hmmsearch -Z 11927849 -E 1000 --cpu 4 HMM pfamseq
|Family (HMM) version:||14|
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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 CPSase_L_D2 domain has been found. There are 191 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 seqence.
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