ID   PRPC_ABDS2              Reviewed;         379 AA.
AC   O34002;
DT   15-JUL-1999, integrated into UniProtKB/Swiss-Prot.
DT   01-JAN-1998, sequence version 1.
DT   13-SEP-2023, entry version 104.
DE   RecName: Full=2-methylcitrate synthase {ECO:0000303|PubMed:9579066};
DE            Short=2-MCS {ECO:0000303|PubMed:9579066};
DE            Short=MCS {ECO:0000303|PubMed:9579066};
DE            EC=2.3.3.5 {ECO:0000269|PubMed:9579066};
DE   AltName: Full=Citrate synthase {ECO:0000303|PubMed:9310359};
DE            EC=2.3.3.16 {ECO:0000269|PubMed:9310359, ECO:0000269|PubMed:9579066};
GN   Name=gltA; Synonyms=cisY;
OS   Antarctic bacterium DS2-3R.
OC   Bacteria.
OX   NCBI_TaxID=56673;
RN   [1]
RP   NUCLEOTIDE SEQUENCE [GENOMIC DNA], PROTEIN SEQUENCE OF 2-16, FUNCTION,
RP   CATALYTIC ACTIVITY, BIOPHYSICOCHEMICAL PROPERTIES, AND SUBUNIT.
RC   STRAIN=DS2-3R;
RX   PubMed=9310359; DOI=10.1111/j.1432-1033.1997.00049.x;
RA   Gerike U., Danson M.J., Russell N.J., Hough D.W.;
RT   "Sequencing and expression of the gene encoding a cold-active citrate
RT   synthase from an Antarctic bacterium, strain DS2-3R.";
RL   Eur. J. Biochem. 248:49-57(1997).
RN   [2]
RP   FUNCTION, CATALYTIC ACTIVITY, BIOPHYSICOCHEMICAL PROPERTIES, INDUCTION, AND
RP   SUBSTRATE SPECIFICITY.
RC   STRAIN=DS2-3R;
RX   PubMed=9579066; DOI=10.1099/00221287-144-4-929;
RA   Gerike U., Hough D.W., Russell N.J., Dyall-Smith M.L., Danson M.J.;
RT   "Citrate synthase and 2-methylcitrate synthase: structural, functional and
RT   evolutionary relationships.";
RL   Microbiology 144:929-935(1998).
RN   [3]
RP   X-RAY CRYSTALLOGRAPHY (2.09 ANGSTROMS) OF 2-379 IN COMPLEX WITH COENZYME A
RP   AND SUBSTRATE, ACTIVE SITE, AND SUBUNIT.
RC   STRAIN=DS2-3R;
RX   PubMed=9551556; DOI=10.1016/s0969-2126(98)00037-9;
RA   Russell R.J., Gerike U., Danson M.J., Hough D.W., Taylor G.L.;
RT   "Structural adaptations of the cold-active citrate synthase from an
RT   Antarctic bacterium.";
RL   Structure 6:351-361(1998).
CC   -!- FUNCTION: Involved in the catabolism of short chain fatty acids (SCFA)
CC       via the tricarboxylic acid (TCA)(acetyl degradation route) and via the
CC       2-methylcitrate cycle I (propionate degradation route). Catalyzes the
CC       Claisen condensation of propionyl-CoA and oxaloacetate (OAA) to yield
CC       2-methylcitrate (2-MC) and CoA. Also catalyzes the condensation of
CC       oxaloacetate with acetyl-CoA but with a lower specificity.
CC       {ECO:0000269|PubMed:9310359, ECO:0000269|PubMed:9579066}.
CC   -!- CATALYTIC ACTIVITY:
CC       Reaction=H2O + oxaloacetate + propanoyl-CoA = (2S,3S)-2-methylcitrate +
CC         CoA + H(+); Xref=Rhea:RHEA:23780, ChEBI:CHEBI:15377,
CC         ChEBI:CHEBI:15378, ChEBI:CHEBI:16452, ChEBI:CHEBI:57287,
CC         ChEBI:CHEBI:57392, ChEBI:CHEBI:58853; EC=2.3.3.5;
CC         Evidence={ECO:0000269|PubMed:9579066};
CC   -!- CATALYTIC ACTIVITY:
CC       Reaction=acetyl-CoA + H2O + oxaloacetate = citrate + CoA + H(+);
CC         Xref=Rhea:RHEA:16845, ChEBI:CHEBI:15377, ChEBI:CHEBI:15378,
CC         ChEBI:CHEBI:16452, ChEBI:CHEBI:16947, ChEBI:CHEBI:57287,
CC         ChEBI:CHEBI:57288; EC=2.3.3.16; Evidence={ECO:0000269|PubMed:9310359,
CC         ECO:0000269|PubMed:9579066};
CC   -!- BIOPHYSICOCHEMICAL PROPERTIES:
CC       Kinetic parameters:
CC         KM=3 uM for oxaloacetate (with propionyl-CoA at pH 8 and 23 degrees
CC         Celsius) {ECO:0000269|PubMed:9579066};
CC         KM=6.9 uM for oxaloacetate (with acetyl-CoA at pH 8 and 23 degrees
CC         Celsius) {ECO:0000269|PubMed:9310359};
CC         KM=7 uM for oxaloacetate (with acetyl-CoA at pH 8 and 23 degrees
CC         Celsius) {ECO:0000269|PubMed:9579066};
CC         KM=16 uM for propionyl-CoA (at pH 8 and 23 degrees Celsius)
CC         {ECO:0000269|PubMed:9579066};
CC         KM=229 uM for acetyl-CoA (at pH 8 and 23 degrees Celsius)
CC         {ECO:0000269|PubMed:9579066};
CC         KM=230 uM for acetyl-CoA (at pH 8 and 23 degrees Celsius)
CC         {ECO:0000269|PubMed:9310359};
CC         Vmax=12 umol/min/mg enzyme with propionyl-CoA as substrate (at pH 8
CC         and 23 degrees Celsius) {ECO:0000269|PubMed:9579066};
CC         Vmax=30 umol/min/mg enzyme with acetyl-CoA as substrate (at pH 8 and
CC         23 degrees Celsius) {ECO:0000269|PubMed:9310359,
CC         ECO:0000269|PubMed:9579066};
CC         Note=kcat is 8 sec(-1) for 2-methylcitrate synthase activity with
CC         propionyl-CoA as substrate (at pH 8 and 23 degrees Celsius). kcat is
CC         21 sec(-1) for citrate synthase activity with acetyl-CoA as substrate
CC         (at pH 8 and 23 degrees Celsius). {ECO:0000269|PubMed:9310359,
CC         ECO:0000269|PubMed:9579066};
CC       Temperature dependence:
CC         Optimum temperature is 31 degrees Celsius. Cold-active. Is rapidly
CC         inactivated at 45 degrees Celsius, and shows significant activity at
CC         10 degrees Celsius and below. {ECO:0000269|PubMed:9310359};
CC   -!- PATHWAY: Organic acid metabolism; propanoate degradation.
CC       {ECO:0000305|PubMed:9579066}.
CC   -!- PATHWAY: Carbohydrate metabolism; tricarboxylic acid cycle; isocitrate
CC       from oxaloacetate: step 1/2. {ECO:0000305|PubMed:9579066}.
CC   -!- SUBUNIT: Homodimer. {ECO:0000269|PubMed:9310359,
CC       ECO:0000269|PubMed:9551556}.
CC   -!- INDUCTION: By growth on propionate, but not acetate or glucose.
CC       {ECO:0000269|PubMed:9579066}.
CC   -!- SIMILARITY: Belongs to the citrate synthase family. {ECO:0000305}.
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DR   EMBL; U85944; AAC45662.1; -; Genomic_DNA.
DR   PDB; 1A59; X-ray; 2.09 A; A=2-379.
DR   PDBsum; 1A59; -.
DR   AlphaFoldDB; O34002; -.
DR   SMR; O34002; -.
DR   DrugBank; DB04272; Citric acid.
DR   DrugBank; DB01992; Coenzyme A.
DR   BRENDA; 2.3.3.1; 15675.
DR   SABIO-RK; O34002; -.
DR   UniPathway; UPA00223; UER00717.
DR   UniPathway; UPA00946; -.
DR   EvolutionaryTrace; O34002; -.
DR   GO; GO:0005737; C:cytoplasm; IEA:InterPro.
DR   GO; GO:0050440; F:2-methylcitrate synthase activity; IDA:UniProtKB.
DR   GO; GO:0036440; F:citrate synthase activity; IDA:UniProtKB.
DR   GO; GO:0019679; P:propionate metabolic process, methylcitrate cycle; IDA:UniProtKB.
DR   GO; GO:0006099; P:tricarboxylic acid cycle; IEA:UniProtKB-UniPathway.
DR   CDD; cd06111; DsCS_like; 1.
DR   Gene3D; 1.10.580.10; Citrate Synthase, domain 1; 1.
DR   Gene3D; 1.10.230.10; Cytochrome P450-Terp, domain 2; 1.
DR   InterPro; IPR011278; 2-MeCitrate/Citrate_synth_II.
DR   InterPro; IPR016142; Citrate_synth-like_lrg_a-sub.
DR   InterPro; IPR016143; Citrate_synth-like_sm_a-sub.
DR   InterPro; IPR002020; Citrate_synthase.
DR   InterPro; IPR019810; Citrate_synthase_AS.
DR   InterPro; IPR024176; Citrate_synthase_bac-typ.
DR   InterPro; IPR036969; Citrate_synthase_sf.
DR   NCBIfam; TIGR01800; cit_synth_II; 1.
DR   PANTHER; PTHR11739; CITRATE SYNTHASE; 1.
DR   PANTHER; PTHR11739:SF4; CITRATE SYNTHASE, PEROXISOMAL; 1.
DR   Pfam; PF00285; Citrate_synt; 1.
DR   PIRSF; PIRSF001369; Citrate_synth; 1.
DR   PRINTS; PR00143; CITRTSNTHASE.
DR   SUPFAM; SSF48256; Citrate synthase; 1.
DR   PROSITE; PS00480; CITRATE_SYNTHASE; 1.
PE   1: Evidence at protein level;
KW   3D-structure; Direct protein sequencing; Transferase;
KW   Tricarboxylic acid cycle.
FT   INIT_MET        1
FT                   /note="Removed"
FT                   /evidence="ECO:0000269|PubMed:9310359"
FT   CHAIN           2..379
FT                   /note="2-methylcitrate synthase"
FT                   /id="PRO_0000169925"
FT   ACT_SITE        222
FT                   /evidence="ECO:0000269|PubMed:9551556"
FT   ACT_SITE        270
FT                   /evidence="ECO:0000269|PubMed:9551556"
FT   ACT_SITE        321
FT                   /evidence="ECO:0000269|PubMed:9551556"
FT   BINDING         187
FT                   /ligand="substrate"
FT                   /evidence="ECO:0000250|UniProtKB:I6Y9Q3"
FT   BINDING         264..268
FT                   /ligand="CoA"
FT                   /ligand_id="ChEBI:CHEBI:57287"
FT                   /evidence="ECO:0000269|PubMed:9551556"
FT   BINDING         279
FT                   /ligand="substrate"
FT                   /evidence="ECO:0000269|PubMed:9551556"
FT   BINDING         346
FT                   /ligand="substrate"
FT                   /evidence="ECO:0000269|PubMed:9551556"
FT   BINDING         365
FT                   /ligand="substrate"
FT                   /evidence="ECO:0000250|UniProtKB:I6Y9Q3"
FT   HELIX           8..10
FT                   /evidence="ECO:0007829|PDB:1A59"
FT   STRAND          19..24
FT                   /evidence="ECO:0007829|PDB:1A59"
FT   TURN            25..28
FT                   /evidence="ECO:0007829|PDB:1A59"
FT   STRAND          29..32
FT                   /evidence="ECO:0007829|PDB:1A59"
FT   HELIX           37..43
FT                   /evidence="ECO:0007829|PDB:1A59"
FT   HELIX           46..55
FT                   /evidence="ECO:0007829|PDB:1A59"
FT   HELIX           61..72
FT                   /evidence="ECO:0007829|PDB:1A59"
FT   HELIX           79..85
FT                   /evidence="ECO:0007829|PDB:1A59"
FT   HELIX           94..107
FT                   /evidence="ECO:0007829|PDB:1A59"
FT   TURN            110..113
FT                   /evidence="ECO:0007829|PDB:1A59"
FT   HELIX           117..142
FT                   /evidence="ECO:0007829|PDB:1A59"
FT   HELIX           156..165
FT                   /evidence="ECO:0007829|PDB:1A59"
FT   HELIX           171..184
FT                   /evidence="ECO:0007829|PDB:1A59"
FT   HELIX           191..200
FT                   /evidence="ECO:0007829|PDB:1A59"
FT   TURN            201..203
FT                   /evidence="ECO:0007829|PDB:1A59"
FT   HELIX           206..218
FT                   /evidence="ECO:0007829|PDB:1A59"
FT   TURN            220..224
FT                   /evidence="ECO:0007829|PDB:1A59"
FT   HELIX           225..235
FT                   /evidence="ECO:0007829|PDB:1A59"
FT   HELIX           244..260
FT                   /evidence="ECO:0007829|PDB:1A59"
FT   HELIX           280..293
FT                   /evidence="ECO:0007829|PDB:1A59"
FT   HELIX           298..314
FT                   /evidence="ECO:0007829|PDB:1A59"
FT   HELIX           321..330
FT                   /evidence="ECO:0007829|PDB:1A59"
FT   HELIX           335..337
FT                   /evidence="ECO:0007829|PDB:1A59"
FT   HELIX           338..359
FT                   /evidence="ECO:0007829|PDB:1A59"
SQ   SEQUENCE   379 AA;  41832 MW;  7D8F4614E3D1CC9F CRC64;
     MTEPTIHKGL AGVTADVTAI SKVNSDTNSL LYRGYPVQEL AAKCSFEQVA YLLWNSELPN
     DSELKAFVNF ERSHRKLDEN VKGAIDLLST ACHPMDVART AVSVLGANHA RAQDSSPEAN
     LEKAMSLLAT FPSVVAYDQR RRRGEELIEP REDLDYSANF LWMTFGEEAA PEVVEAFNVS
     MILYAEHSFN ASTFTARVIT STLADLHSAV TGAIGALKGP LHGGANEAVM HTFEEIGIRK
     DESLDEAATR SKAWMVDALA QKKKVMGFGH RVYKNGDSRV PTMKSALDAM IKHYDRPEML
     GLYNGLEAAM EEAKQIKPNL DYPAGPTYNL MGFDTEMFTP LFIAARITGW TAHIMEQVAD
     NALIRPLSEY NGPEQRQVP
//