EzCatDB: D00256

DB codeD00256
CATH domainDomain 11.10.580.10Catalytic domain
Domain 21.10.230.10Catalytic domain
E.C.2.3.3.1
CSA1aj8,1al6
MACiEM0078


Enzyme Name
Swiss-protKEGG

Q53554P23007P00889
Protein nameCitrate synthaseCitrate synthase, mitochondrialCitrate synthase, mitochondrialcitrate (Si)-synthase
(R)-citric synthase
citrate condensing enzyme
citrate oxaloacetate-lyase [(pro-3S)-CH2COO-->acetyl-CoA]
citrate oxaloacetate-lyase, CoA-acetylating
citrate synthase
citrate synthetase
citric synthase
citric-condensing enzyme
citrogenase
condensing enzyme
oxaloacetate transacetase
oxalacetic transacetase
SynonymsEC 2.3.3.1
EC 2.3.3.1
EC 2.3.3.1

KEGG pathways
MAP codePathways
MAP00020Citrate cycle (TCA cycle)
MAP00630Glyoxylate and dicarboxylate metabolism

Swiss-prot:Accession NumberQ53554P23007P00889
Entry nameCISY_PYRFUCISY_CHICKCISY_PIG
ActivityAcetyl-CoA + H(2)O + oxaloacetate = citrate + CoA.Acetyl-CoA + H(2)O + oxaloacetate = citrate + CoA.Acetyl-CoA + H(2)O + oxaloacetate = citrate + CoA.
SubunitHomodimer.Homodimer.Homodimer.
Subcellular location
Mitochondrion matrix.Mitochondrion matrix.
Cofactor




SubstratesProductsintermediates
KEGG-idC00024C00001C00036C00010C00158
C00566
CompoundAcetyl-CoAH2OOxaloacetateCoACitrateEnolic acetyl-CoACitryl-CoAEnzyme-anhydride intermediate
Typeamine group,carbohydrate,nucleotide,peptide/protein,sulfide groupH2Ocarbohydrate,carboxyl groupamine group,carbohydrate,nucleotide,peptide/protein,sulfhydryl groupcarbohydrate,carboxyl group


1aj8A01Unbound
UnboundUnboundUnbound
Unbound
1aj8B01Unbound
UnboundUnboundUnbound
Unbound
1al6A01Unbound
UnboundUnboundUnbound
Unbound
1amzA01Unbound
UnboundUnboundUnbound
Unbound
1cscA01Unbound
UnboundUnboundUnbound
Unbound
1cshA01Unbound
UnboundUnboundUnbound
Unbound
1csiA01Unbound
UnboundUnboundUnbound
Unbound
1csrA01Unbound
UnboundUnboundUnbound
Unbound
1cssA01Unbound
UnboundUnboundUnbound
Unbound
2cscA01Unbound
UnboundUnboundUnbound
Unbound
3cscA01Unbound
UnboundUnboundUnbound
Unbound
4cscA01Unbound
UnboundUnboundUnbound
Unbound
5cscA01Unbound
UnboundUnboundUnbound
Unbound
5cscB01Unbound
UnboundUnboundUnbound
Unbound
5ctsA01Unbound
UnboundUnboundUnbound
Unbound
6cscA01Unbound
UnboundUnboundUnbound
Unbound
6cscB01Unbound
UnboundUnboundUnbound
Unbound
6ctsA01Unbound
UnboundUnboundUnbound
Unbound
1ctsA01Unbound
UnboundUnboundUnbound
Unbound
2ctsA01Unbound
UnboundUnboundUnbound
Unbound
4ctsA01Unbound
UnboundUnboundUnbound
Unbound
4ctsB01Unbound
UnboundUnboundUnbound
Unbound
1aj8A02Unbound
UnboundBound:COABound:CIT
Unbound
1aj8B02Unbound
UnboundBound:COABound:CIT
Unbound
1al6A02Analogue:HAX
Bound:OAAUnboundUnbound
Unbound
1amzA02Analogue:NMX
Analogue:MLTUnboundUnbound
Unbound
1cscA02Analogue:CMC
Analogue:MALUnboundUnbound
Unbound
1cshA02Analogue:AMX
Bound:OAAUnboundUnbound
Unbound
1csiA02Analogue:CMX
Bound:OAAUnboundUnbound
Unbound
1csrA02Analogue:FAM
Bound:OAAUnboundUnbound
Unbound
1cssA02Analogue:FCX
Bound:OAAUnboundUnbound
Unbound
2cscA02Analogue:CMC
Analogue:MALUnboundUnbound
Unbound
3cscA02Bound:ACO
Analogue:MALUnboundUnbound
Unbound
4cscA02Bound:ACO
Analogue:MALUnboundUnbound
Unbound
5cscA02Unbound
UnboundUnboundUnbound
Unbound
5cscB02Unbound
UnboundUnboundUnbound
Unbound
5ctsA02Analogue:CMC
Bound:OAAUnboundUnbound
Unbound
6cscA02Analogue:COF
UnboundUnboundBound:CIT
Unbound
6cscB02Analogue:COF
UnboundUnboundBound:CIT
Unbound
6ctsA02Unbound
UnboundUnboundUnbound
Intermediate-analogue:CIC
1ctsA02Unbound
UnboundUnboundUnbound
Unbound
2ctsA02Unbound
UnboundBound:COABound:CIT
Unbound
4ctsA02Unbound
Bound:OAAUnboundUnbound
Unbound
4ctsB02Unbound
Bound:OAAUnboundUnbound
Unbound

Active-site residues
resource
Swiss-prot;P23007, P00889, Q53554
pdbCatalytic residuesModified residues
1aj8A01HIS 223

1aj8B01HIS 223

1al6A01HIS 274

1amzA01HIS 274

1cscA01HIS 274

1cshA01HIS 274

1csiA01HIS 274

1csrA01HIS 274

1cssA01HIS 274

2cscA01HIS 274

3cscA01HIS 274

4cscA01HIS 274

5cscA01HIS 274

5cscB01HIS 274

5ctsA01HIS 274

6cscA01HIS 274

6cscB01HIS 274

6ctsA01HIS 274

1ctsA01HIS 274

2ctsA01HIS 274

4ctsA01HIS 274

4ctsB01HIS 274

1aj8A02HIS 262;ASP 312

1aj8B02HIS 262;ASP 312

1al6A02HIS 320;ASP 375

1amzA02HIS 320;ASP 375

1cscA02HIS 320;ASP 375

1cshA02HIS 320;ASP 375

1csiA02HIS 320;ASP 375

1csrA02HIS 320;ASP 375

1cssA02HIS 320;ASP 375

2cscA02HIS 320;ASP 375

3cscA02HIS 320;ASP 375

4cscA02HIS 320;ASP 375

5cscA02HIS 320;ASP 375

5cscB02HIS 320;ASP 375

5ctsA02HIS 320;ASP 375

6cscA02HIS 320;ASP 375

6cscB02HIS 320;ASP 375

6ctsA02HIS 320;ASP 375

1ctsA02HIS 320;ASP 375
LYS 368(N6,N6,N6-trimethyllysine)
2ctsA02HIS 320;ASP 375
LYS 368(N6,N6,N6-trimethyllysine)
4ctsA02HIS 320;ASP 375
LYS 368(N6,N6,N6-trimethyllysine)
4ctsB02HIS 320;ASP 375
LYS 368(N6,N6,N6-trimethyllysine)

References for Catalytic Mechanism
ReferencesSectionsNo. of steps in catalysis
[6]p.149-150
[7]Scheme 2, p.6712
[14]Fig.3, p.7561-75624
[15]Fig.4, p.22162
[16]Scheme 3, p.711-7123
[17]Scheme 2, p.524-5263
[18]p.6030
[21]p.7912-7914
[22]p.7906-7907
[23]Scheme 2, Scheme 3, Scheme 4, p.2265
[27]p.769-770
[29]Fig.2, p.7757-77593
[35]Fig.1, p.10667-106713
[39]p.9987
[45]


references
[1]
PubMed ID1278369
JournalFEBS Lett
Year1976
Volume62
Pages281-3
AuthorsWiegand G
TitleCrystallization and preliminary x-ray data of well-ordered crystals from pig heart citrate synthase.
[2]
PubMed ID666830
JournalBiochem Biophys Res Commun
Year1978
Volume82
Pages150-6
AuthorsWang AH, Sherman ML, Rich A
TitleA crystallographic investigation of citrate synthase from pig and chicken heart muscle.
[3]
PubMed ID224920
JournalBiochemistry
Year1979
Volume18
Pages3822-7
AuthorsWeidman SW, Drysdale GR
TitleInteraction of a paramagnetic analogue of oxaloacetate with citrate synthase.
[4]
PubMed ID436830
JournalEur J Biochem
Year1979
Volume93
Pages41-50
AuthorsWiegand G, Kukla D, Scholze H, Jones TA, Huber R
TitleCrystal structure analysis of the tetragonal crystal form are preliminary molecular model of pig-heart citrate synthase.
[5]
PubMed ID218954
JournalJ Biol Chem
Year1979
Volume254
Pages2800-6
AuthorsCaggiano AV, Powell GL
TitleRegulation of enzymes by fatty acyl coenzyme A. Site-specific binding of fatty acyl coenzyme A by citrate synthase--a spin-labeling study.
[6]
CommentsX-RAY CRYSTALLOGRAPHY (2.7 AND 1.7 ANGSTROMS).
Medline ID83010291
PubMed ID7120407
JournalJ Mol Biol
Year1982
Volume158
Pages111-52
AuthorsRemington S, Wiegand G, Huber R
TitleCrystallographic refinement and atomic models of two different forms of citrate synthase at 2.7 and 1.7 A resolution.
Related PDB1cts,2cts
Related Swiss-protP00889
[7]
PubMed ID6861748
JournalEur J Biochem
Year1983
Volume133
Pages665-72
AuthorsLohlein-Werhahn G, Bayer E, Bauer B, Eggerer H
TitleHysteretic behaviour of citrate synthase. Alternating sites during the catalytic cycle.
[8]
PubMed ID6337135
JournalJ Biol Chem
Year1983
Volume258
Pages1297-8
AuthorsRubin BH, Stallings WC, Glusker JP, Bayer ME, Janin J, Srere PA
TitleCrystallographic studies of Escherichia coli citrate synthase.
[9]
CommentsX-ray crystallography
PubMed ID6716477
JournalJ Mol Biol
Year1984
Volume174
Pages205-19
AuthorsWiegand G, Remington S, Deisenhofer J, Huber R
TitleCrystal structure analysis and molecular model of a complex of citrate synthase with oxaloacetate and S-acetonyl-coenzyme A.
Related PDB4cts
[10]
PubMed ID3978085
JournalBiochemistry
Year1985
Volume24
Pages452-7
AuthorsKurz LC, Ackerman JJ, Drysdale GR
TitleEvidence from 13C NMR for polarization of the carbonyl of oxaloacetate in the active site of citrate synthase.
[11]
PubMed ID3607038
JournalBiochemistry
Year1987
Volume26
Pages2623-7
AuthorsKurz LC, Drysdale GR
TitleEvidence from Fourier transform infrared spectroscopy for polarization of the carbonyl of oxaloacetate in the active site of citrate synthase.
[12]
PubMed ID2731546
JournalEur J Biochem
Year1989
Volume182
Pages119-24
AuthorsPettersson G, Lill U, Eggerer H
TitleMechanism of interaction of citrate synthase with citryl-CoA.
[13]
PubMed ID2276456
JournalBiochem Soc Trans
Year1990
Volume18
Pages596-7
AuthorsIles RA, Davies SE, Chalmers RA, Wharton CW, White A, Sreedharan S, Phillips I, Brocklehurst K
TitleStructural and mechanistic studies on citrate synthase by nuclear magnetic resonance and Fourier transform infra-red spectroscopies.
[14]
CommentsMUTAGENESIS.
Medline ID91104711
PubMed ID1702991
JournalBiochemistry
Year1990
Volume29
Pages7557-63
AuthorsAlter GM, Casazza JP, Zhi W, Nemeth P, Srere PA, Evans CT
TitleMutation of essential catalytic residues in pig citrate synthase.
Related Swiss-protP00889
[15]
CommentsTISSUE=Heart muscle;
Medline ID90248434
PubMed ID2337600
JournalBiochemistry
Year1990
Volume29
Pages2213-9
AuthorsKarpusas M, Branchaud B, Remington SJ
TitleProposed mechanism for the condensation reaction of citrate synthase: 1.9-A structure of the ternary complex with oxaloacetate and carboxymethyl coenzyme A.
Related PDB5cts,6cts
Related Swiss-protP23007
[16]
PubMed ID2206458
JournalBiol Chem Hoppe Seyler
Year1990
Volume371
Pages707-13
AuthorsWilde J, Lill U, Eggerer H
TitleOn the action of carboxy groups in the citrate synthase reaction.
[17]
PubMed ID1684105
JournalBiochem J
Year1991
Volume280
Pages521-6
AuthorsMan WJ, Li Y, O'Connor CD, Wilton DC
TitleConversion of citrate synthase into citryl-CoA lyase as a result of mutation of the active-site aspartic acid residue to glutamic acid.
[18]
CommentsX-ray crystallography
PubMed ID2043640
JournalBiochemistry
Year1991
Volume30
Pages6024-31
AuthorsKarpusas M, Holland D, Remington SJ
Title1.9-A structures of ternary complexes of citrate synthase with D- and L-malate: mechanistic implications.
Related PDB1csc,2csc,3csc,4csc
[19]
CommentsX-RAY CRYSTALLOGRAPHY (2.8 ANGSTROMS) OF OPEN CONFORMATION.
Medline ID91255228
PubMed ID2043641
JournalBiochemistry
Year1991
Volume30
Pages6031-6
AuthorsLiao DI, Karpusas M, Remington SJ
TitleCrystal structure of an open conformation of citrate synthase from chicken heart at 2.8-A resolution.
Related PDB5csc
Related Swiss-protP23007
[20]
PubMed ID1939121
JournalJ Biol Chem
Year1991
Volume266
Pages20709-13
AuthorsDonald LJ, Crane BR, Anderson DH, Duckworth HW
TitleThe role of cysteine 206 in allosteric inhibition of Escherichia coli citrate synthase. Studies by chemical modification, site-directed mutagenesis, and 19F NMR.
[21]
PubMed ID1324723
JournalBiochemistry
Year1992
Volume31
Pages7908-14
AuthorsKurz LC, Drysdale GR, Riley MC, Evans CT, Srere PA
TitleCatalytic strategy of citrate synthase: effects of amino acid changes in the acetyl-CoA binding site on transition-state analog inhibitor complexes.
[22]
PubMed ID1324722
JournalBiochemistry
Year1992
Volume31
Pages7899-907
AuthorsKurz LC, Shah S, Crane BR, Donald LJ, Duckworth HW, Drysdale GR
TitleProton uptake accompanies formation of the ternary complex of citrate synthase, oxaloacetate, and the transition-state analog inhibitor, carboxymethyl-CoA. Evidence that a neutral enol is the activated form of acetyl-CoA in the citrate synthase reaction.
[23]
PubMed ID1499334
JournalCurr Top Cell Regul
Year1992
Volume33
Pages209-29
AuthorsRemington SJ
TitleStructure and mechanism of citrate synthase.
[24]
PubMed ID8098211
JournalBiochem J
Year1993
Volume291
Pages927-32
AuthorsEvans CT, Sumegi B, Srere PA, Sherry AD, Malloy CR
Title13C]propionate oxidation in wild-type and citrate synthase mutant Escherichia coli: evidence for multiple pathways of propionate utilization.
[25]
PubMed ID8331668
JournalJ Mol Biol
Year1993
Volume232
Pages308-9
AuthorsRussell RJ, Byrom D, Danson MJ, Hough DW, Taylor GL
TitleCrystallization and preliminary crystallographic study of citrate synthase from the thermophilic Archaeon Thermoplasma acidophilum.
[26]
PubMed ID8356034
JournalProteins
Year1993
Volume16
Pages393-407
AuthorsEch-Cherif el-Kettani MA, Zakrzewska K, Durup J, Lavery R
TitleAn analysis of the conformational paths of citrate synthase.
[27]
PubMed ID8010958
JournalBiochem J
Year1994
Volume300
Pages765-70
AuthorsMan WJ, Li Y, O'Connor CD, Wilton DC
TitleThe effect of replacing the conserved active-site residues His-264, Asp-312 and Arg-314 on the binding and catalytic properties of Escherichia coli citrate synthase.
[28]
PubMed ID7918384
JournalBiochemistry
Year1994
Volume33
Pages11684-91
AuthorsLindbladh C, Brodeur RD, Small WC, Lilius G, Bulow L, Mosbach K, Srere PA
TitleMetabolic studies on Saccharomyces cerevisiae containing fused citrate synthase/malate dehydrogenase.
[29]
CommentsX-ray crystallography
PubMed ID8011640
JournalBiochemistry
Year1994
Volume33
Pages7753-9
AuthorsUsher KC, Remington SJ, Martin DP, Drueckhammer DG
TitleA very short hydrogen bond provides only moderate stabilization of an enzyme-inhibitor complex of citrate synthase.
Related PDB1csh,1csi
[30]
PubMed ID8276829
JournalJ Biol Chem
Year1994
Volume269
Pages412-7
AuthorsPereira DS, Donald LJ, Hosfield DJ, Duckworth HW
TitleActive site mutants of Escherichia coli citrate synthase. Effects of mutations on catalytic and allosteric properties.
[31]
PubMed ID7704526
JournalStructure
Year1994
Volume2
Pages1157-67
AuthorsRussell RJ, Hough DW, Danson MJ, Taylor GL
TitleThe crystal structure of citrate synthase from the thermophilic archaeon, Thermoplasma acidophilum.
[32]
PubMed ID7577912
JournalBiochemistry
Year1995
Volume34
Pages13278-88
AuthorsKurz LC, Shah S, Frieden C, Nakra T, Stein RE, Drysdale GR, Evans CT, Srere PA
TitleCatalytic strategy of citrate synthase: subunit interactions revealed as a consequence of a single amino acid change in the oxaloacetate binding site.
[33]
CommentsX-ray crystallography
PubMed ID7492547
JournalBiochemistry
Year1995
Volume34
Pages15459-66
AuthorsSchwartz B, Drueckhammer DG, Usher KC, Remington SJ
Titlealpha-Fluoro acid and alpha-fluoro amide analogs of acetyl-CoA as inhibitors of citrate synthase: effect of pKa matching on binding affinity and hydrogen bond length.
Related PDB1csr,1css
[34]
PubMed ID9052973
JournalJ Mol Recognit
Year1995
Volume8
Pages327-33
AuthorsEvans CT
TitleMetabolic engineering of a non-allosteric citrate synthase in an Escherichia coli citrate synthase mutant.
[35]
PubMed ID8718855
JournalBiochemistry
Year1996
Volume35
Pages10661-72
AuthorsEvans CT, Kurz LC, Remington SJ, Srere PA
TitleActive site mutants of pig citrate synthase: effects of mutations on the enzyme catalytic and structural properties.
[36]
PubMed ID8979399
JournalPlant Cell Physiol
Year1996
Volume37
Pages1022-9
AuthorsLa Cognata U, Landschutze V, Willmitzer L, Muller-Rober B
TitleStructure and expression of mitochondrial citrate synthases from higher plants.
[37]
PubMed ID9388613
JournalBiochem Soc Trans
Year1997
Volume25
Pages380S
AuthorsSevercan F, Stenland C, Millhauser G
TitleESR studies of pig citrate synthase.
[38]
CommentsX-ray crystallography
PubMed ID9092828
JournalBiochemistry
Year1997
Volume36
Pages3981-90
AuthorsKurz LC, Roble JH, Nakra T, Drysdale GR, Buzan JM, Schwartz B, Drueckhammer DG
TitleAbility of single-site mutants of citrate synthase to catalyze proton transfer from the methyl group of dethiaacetyl-coenzyme A, a non-thioester substrate analog.
Related PDB1al6,1amz
[39]
CommentsX-RAY CRYSTALLOGRAPHY (1.9 ANGSTROMS).
Medline ID97400454
PubMed ID9254593
JournalBiochemistry
Year1997
Volume36
Pages9983-94
AuthorsRussell RJ, Ferguson JM, Hough DW, Danson MJ, Taylor GL
TitleThe crystal structure of citrate synthase from the hyperthermophilic archaeon pyrococcus furiosus at 1.9 A resolution,.
Related PDB1aj8
Related Swiss-protQ53554
[40]
PubMed ID9757123
JournalActa Crystallogr D Biol Crystallogr
Year1998
Volume54
Pages1012-3
AuthorsGerike U, Russell RJ, Danson MJ, Russell NJ, Hough DW, Taylor GL
TitlePreliminary crystallographic studies of citrate synthase from an Antarctic psychrotolerant bacterium.
[41]
PubMed ID9657685
JournalBiochemistry
Year1998
Volume37
Pages9724-37
AuthorsKurz LC, Nakra T, Stein R, Plungkhen W, Riley M, Hsu F, Drysdale GR
TitleEffects of changes in three catalytic residues on the relative stabilities of some of the intermediates and transition states in the citrate synthase reaction.
[42]
PubMed ID10387046
JournalBiochemistry
Year1999
Volume38
Pages8022-31
AuthorsGu Z, Drueckhammer DG, Kurz L, Liu K, Martin DP, McDermott A
TitleSolid state NMR studies of hydrogen bonding in a citrate synthase inhibitor complex.
[43]
PubMed ID9893982
JournalBiochemistry
Year1999
Volume38
Pages881-9
AuthorsShatalin K, Lebreton S, Rault-Leonardon M, Velot C, Srere PA
TitleElectrostatic channeling of oxaloacetate in a fusion protein of porcine citrate synthase and porcine mitochondrial malate dehydrogenase.
[44]
PubMed ID9933583
JournalJ Biol Chem
Year1999
Volume274
Pages3941-5
AuthorsHaggie PM, Brindle KM
TitleMitochondrial citrate synthase is immobilized in vivo.
[45]
PubMed ID10694395
JournalBiochemistry
Year2000
Volume39
Pages2283-96
AuthorsKurz LC, Drysdale G, Riley M, Tomar MA, Chen J, Russell RJ, Danson MJ
TitleKinetics and mechanism of the citrate synthase from the thermophilic archaeon Thermoplasma acidophilum.
[46]
PubMed ID11501994
JournalJ Mol Biol
Year2001
Volume310
Pages1039-53
AuthorsRoccatano D, Mark AE, Hayward S
TitleInvestigation of the mechanism of domain closure in citrate synthase by molecular dynamics simulation.
[47]
PubMed ID11707611
JournalProtein Eng
Year2001
Volume14
Pages655-61
AuthorsGerike U, Danson MJ, Hough DW
TitleCold-active citrate synthase: mutagenesis of active-site residues.

comments
This enzyme catalyzes the following reactions sequentially:
(A) Isomerization (enolization)
(B) Condensation (Addition)
(C) Hydrolysis of thioester group

createdupdated
2004-06-012009-02-26


Copyright: Nozomi Nagano, JST & CBRC-AIST
Funded by PRESTO/Japan Science and Technology Corporation (JST) (December 2001 - November 2004)
Funded by Grant-in-Aid for Publication of Scientific Research Results/Japan Society for the Promotion of Science (JSPS) (April 2005 - March 2006)
Funded by Grant-in-Aid for Scientific Research (B)/Japan Society for the Promotion of Science (JSPS) (April 2005 - March 2008)
Funded by BIRD/Japan Science and Technology Corporation (JST) (September 2005 - September 2010)
Funded by BIRD/Japan Science and Technology Corporation (JST) (October 2007 - September 2010)
Funded by Grant-in-Aid for Publication of Scientific Research Results/Japan Society for the Promotion of Science (JSPS) (April 2011 - March 2012)

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