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281  structures 7581  species 0  interactions 18200  sequences 121  architectures

Family: Citrate_synt (PF00285)

Summary: Citrate synthase, C-terminal domain

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This is the Wikipedia entry entitled "Citrate synthase family". More...

Citrate synthase family Edit Wikipedia article

Citrate_synt
PDB 1a59 EBI.jpg
cold-active citrate synthase
Identifiers
SymbolCitrate_synt
PfamPF00285
InterProIPR002020
PROSITEPDOC00422
SCOPe1csc / SUPFAM
CDDcd06101

In molecular biology, the citrate synthase family of proteins includes the enzymes citrate synthase EC 2.3.3.1, and the related enzymes 2-methylcitrate synthase EC 2.3.3.5 and ATP citrate lyase EC 2.3.3.8.

Citrate synthase is a member of a small family of enzymes that can directly form a carbon-carbon bond without the presence of metal ion cofactors. It catalyses the first reaction in the Krebs' cycle, namely the conversion of oxaloacetate and acetyl-coenzyme A into citrate and coenzyme A. This reaction is important for energy generation and for carbon assimilation. The reaction proceeds via a non-covalently bound citryl-coenzyme A intermediate in a 2-step process (aldol-Claisen condensation followed by the hydrolysis of citryl-CoA).

Citrate synthase enzymes are found in two distinct structural types: type I enzymes (found in eukaryotes, Gram-positive bacteria and archaea) form homodimers and have shorter sequences than type II enzymes, which are found in Gram-negative bacteria and are hexameric in structure. In both types, the monomer is composed of two domains: a large alpha-helical domain consisting of two structural repeats, where the second repeat is interrupted by a small alpha-helical domain. The cleft between these domains forms the active site, where both citrate and acetyl-coenzyme A bind. The enzyme undergoes a conformational change upon binding of the oxaloacetate ligand, whereby the active site cleft closes over in order to form the acetyl-CoA binding site.[1] The energy required for domain closure comes from the interaction of the enzyme with the substrate. Type II enzymes possess an extra N-terminal beta-sheet domain, and some type II enzymes are allosterically inhibited by NADH.[2]

2-methylcitrate synthase catalyses the conversion of oxaloacetate and propanoyl-CoA into (2R,3S)-2-hydroxybutane-1,2,3-tricarboxylate and coenzyme A. This enzyme is induced during bacterial growth on propionate, while type II hexameric citrate synthase is constitutive.[3]

ATP citrate lyase catalyses the Mg.ATP-dependent, CoA-dependent cleavage of citrate into oxaloacetate and acetyl-CoA, a key step in the reductive tricarboxylic acid pathway of CO2 assimilation used by a variety of autotrophic bacteria and archaea to fix carbon dioxide.[4] ATP citrate lyase is composed of two distinct subunits. In eukaryotes, ATP citrate lyase is a homotetramer of a single large polypeptide, and is used to produce cytosolic acetyl-CoA from mitochondrial produced citrate.[5]

References

  1. ^ Daidone I, Roccatano D, Hayward S (June 2004). "Investigating the accessibility of the closed domain conformation of citrate synthase using essential dynamics sampling". J. Mol. Biol. 339 (3): 515–25. doi:10.1016/j.jmb.2004.04.007. PMID 15147839.
  2. ^ Francois JA, Starks CM, Sivanuntakorn S, Jiang H, Ransome AE, Nam JW, Constantine CZ, Kappock TJ (November 2006). "Structure of a NADH-insensitive hexameric citrate synthase that resists acid inactivation". Biochemistry. 45 (45): 13487–99. doi:10.1021/bi061083k. PMID 17087502.
  3. ^ Gerike U, Hough DW, Russell NJ, Dyall-Smith ML, Danson MJ (April 1998). "Citrate synthase and 2-methylcitrate synthase: structural, functional and evolutionary relationships". Microbiology. 144 (4): 929–35. doi:10.1099/00221287-144-4-929. PMID 9579066.
  4. ^ Kim W, Tabita FR (September 2006). "Both subunits of ATP-citrate lyase from Chlorobium tepidum contribute to catalytic activity". J. Bacteriol. 188 (18): 6544–52. doi:10.1128/JB.00523-06. PMC 1595482. PMID 16952946.
  5. ^ Bauer DE, Hatzivassiliou G, Zhao F, Andreadis C, Thompson CB (September 2005). "ATP citrate lyase is an important component of cell growth and transformation". Oncogene. 24 (41): 6314–22. doi:10.1038/sj.onc.1208773. PMID 16007201.
This article incorporates text from the public domain Pfam and InterPro: IPR002020

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Citrate synthase, C-terminal domain Provide feedback

This is the long, C-terminal part of the enzyme.

External database links

This tab holds annotation information from the InterPro database.

InterPro entry IPR002020

Citrate synthase EC is a member of a small family of enzymes that can directly form a carbon-carbon bond without the presence of metal ion cofactors. It catalyses the first reaction in the Krebs' cycle, namely the conversion of oxaloacetate and acetyl-coenzyme A into citrate and coenzyme A. This reaction is important for energy generation and for carbon assimilation. The reaction proceeds via a non-covalently bound citryl-coenzyme A intermediate in a 2-step process (aldol-Claisen condensation followed by the hydrolysis of citryl-CoA).

Citrate synthase enzymes are found in two distinct structural types: type I enzymes (found in eukaryotes, Gram-positive bacteria and archaea) form homodimers and have shorter sequences than type II enzymes, which are found in Gram-negative bacteria and are hexameric in structure. In both types, the monomer is composed of two domains: a large alpha-helical domain consisting of two structural repeats, where the second repeat is interrupted by a small alpha-helical domain. The cleft between these domains forms the active site, where both citrate and acetyl-coenzyme A bind. The enzyme undergoes a conformational change upon binding of the oxaloacetate ligand, whereby the active site cleft closes over in order to form the acetyl-CoA binding site [ PUBMED:15147839 ]. The energy required for domain closure comes from the interaction of the enzyme with the substrate. Type II enzymes possess an extra N-terminal beta-sheet domain, and some type II enzymes are allosterically inhibited by NADH [ PUBMED:17087502 ].

This entry represents types I and II citrate synthase enzymes, as well as the related enzymes 2-methylcitrate synthase and ATP citrate synthase. 2-methylcitrate ( EC ) synthase catalyses the conversion of oxaloacetate and propanoyl-CoA into (2R,3S)-2-hydroxybutane-1,2,3-tricarboxylate and coenzyme A. This enzyme is induced during bacterial and fungal growth on propionate [ PUBMED:17973657 ], while type II hexameric citrate synthase is constitutive [ PUBMED:9579066 ]. ATP citrate synthase ( EC ) (also known as ATP citrate lyase) catalyses the MgATP-dependent, CoA-dependent cleavage of citrate into oxaloacetate and acetyl-CoA, a key step in the reductive tricarboxylic acid pathway of CO2 assimilation used by a variety of autotrophic bacteria and archaea to fix carbon dioxide [ PUBMED:16952946 ]. ATP citrate synthase is composed of two distinct subunits. In eukaryotes, ATP citrate synthase is a homotetramer of a single large polypeptide, and is used to produce cytosolic acetyl-CoA from mitochondrial produced citrate [ PUBMED:16007201 ]. This entry includes citrate synthase from Thermosulfidibacter takaii, which catalyses both citrate generation and citrate cleavage as it is part of a reversible tricarboxylic acid (TCA) cycle that can fix carbon dioxide autotrophically and may represent an ancestral mode of the conventional reductive TCA (rTCA) cycle [ PUBMED:29420286 ].

Gene Ontology

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Domain organisation

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Alignments

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  Seed
(722)
Full
(18200)
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(79038)
RP15
(2548)
RP35
(8307)
RP55
(17321)
RP75
(29413)
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  Seed
(722)
Full
(18200)
Representative proteomes UniProt
(79038)
RP15
(2548)
RP35
(8307)
RP55
(17321)
RP75
(29413)
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  Seed
(722)
Full
(18200)
Representative proteomes UniProt
(79038)
RP15
(2548)
RP35
(8307)
RP55
(17321)
RP75
(29413)
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Curation and family details

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Seed source: Prosite
Previous IDs: citrate_synt;
Type: Domain
Sequence Ontology: SO:0000417
Author: Finn RD
Number in seed: 722
Number in full: 18200
Average length of the domain: 322.20 aa
Average identity of full alignment: 29 %
Average coverage of the sequence by the domain: 72.47 %

HMM information View help on HMM parameters

HMM build commands:
build method: hmmbuild -o /dev/null HMM SEED
search method: hmmsearch -Z 57096847 -E 1000 --cpu 4 HMM pfamseq
Model details:
Parameter Sequence Domain
Gathering cut-off 21.8 21.8
Trusted cut-off 21.8 21.8
Noise cut-off 21.7 21.7
Model length: 360
Family (HMM) version: 23
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Species distribution

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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 Citrate_synt domain has been found. There are 281 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
A0A0P0Y2X7 View 3D Structure Click here
A0A0P0Y4G2 View 3D Structure Click here
A0A0R0G0M9 View 3D Structure Click here
A0A1D6FHT8 View 3D Structure Click here
A0A1D6H4C4 View 3D Structure Click here
A0A1D6H4C4 View 3D Structure Click here
A0A1D6H6F1 View 3D Structure Click here
A0A1D6MRM3 View 3D Structure Click here
A0A1D6QRH8 View 3D Structure Click here
A0A1D8PSH3 View 3D Structure Click here
A4HXU4 View 3D Structure Click here
A4HXU5 View 3D Structure Click here
B4FIC0 View 3D Structure Click here
C6KST9 View 3D Structure Click here
F1QZ09 View 3D Structure Click here
I1JJ62 View 3D Structure Click here
I1KMR0 View 3D Structure Click here
I1KTQ4 View 3D Structure Click here
I1KY39 View 3D Structure Click here
I1M6V7 View 3D Structure Click here
I1MGE7 View 3D Structure Click here
I1MJI9 View 3D Structure Click here
I1MRQ9 View 3D Structure Click here
I6Y9Q3 View 3D Structure Click here
K7LBM2 View 3D Structure Click here
K7MR36 View 3D Structure Click here
O75390 View 3D Structure Click here
P00890 View 3D Structure Click here
P08679 View 3D Structure Click here
P0ABH7 View 3D Structure Click here
P16638 View 3D Structure Click here
P20115 View 3D Structure Click here
P31660 View 3D Structure Click here
P34575 View 3D Structure Click here
P43635 View 3D Structure Click here
P53396 View 3D Structure Click here
P53585 View 3D Structure Click here
P90731 View 3D Structure Click here
P9WPD3 View 3D Structure Click here
P9WPD5 View 3D Structure Click here
Q10306 View 3D Structure Click here
Q2FXN3 View 3D Structure Click here
Q4CVJ5 View 3D Structure Click here
Q4E5I4 View 3D Structure Click here
Q54KL0 View 3D Structure Click here
Q54YA0 View 3D Structure Click here
Q553V1 View 3D Structure Click here
Q6EUF8 View 3D Structure Click here
Q7F8R1 View 3D Structure Click here
Q7KN85 View 3D Structure Click here
Q7ZVY5 View 3D Structure Click here
Q80X68 View 3D Structure Click here
Q86AV6 View 3D Structure Click here
Q8I6U7 View 3D Structure Click here
Q8MQU6 View 3D Structure Click here
Q8VHF5 View 3D Structure Click here
Q91V92 View 3D Structure Click here
Q93VT8 View 3D Structure Click here
Q95TZ4 View 3D Structure Click here
Q9C522 View 3D Structure Click here
Q9CZU6 View 3D Structure Click here
Q9FGX1 View 3D Structure Click here
Q9LXS6 View 3D Structure Click here
Q9LXS7 View 3D Structure Click here
Q9M1D3 View 3D Structure Click here
Q9P7W3 View 3D Structure Click here
Q9SJH7 View 3D Structure Click here
Q9W401 View 3D Structure Click here
R4GEU0 View 3D Structure Click here