PRPC_ASPFC
ID PRPC_ASPFC Reviewed; 465 AA.
AC B0YD89;
DT 29-APR-2015, integrated into UniProtKB/Swiss-Prot.
DT 08-APR-2008, sequence version 1.
DT 03-AUG-2022, entry version 73.
DE RecName: Full=2-methylcitrate synthase, mitochondrial {ECO:0000305};
DE Short=Methylcitrate synthase {ECO:0000303|PubMed:17973657};
DE EC=2.3.3.5 {ECO:0000269|PubMed:17973657};
DE AltName: Full=(2S,3S)-2-methylcitrate synthase {ECO:0000250|UniProtKB:P31660};
DE AltName: Full=Citrate synthase 2 {ECO:0000305};
DE EC=2.3.3.16 {ECO:0000269|PubMed:17973657};
DE Flags: Precursor;
GN Name=mcsA {ECO:0000303|PubMed:17973657}; ORFNames=AFUB_094700;
OS Neosartorya fumigata (strain CEA10 / CBS 144.89 / FGSC A1163) (Aspergillus
OS fumigatus).
OC Eukaryota; Fungi; Dikarya; Ascomycota; Pezizomycotina; Eurotiomycetes;
OC Eurotiomycetidae; Eurotiales; Aspergillaceae; Aspergillus;
OC Aspergillus subgen. Fumigati.
OX NCBI_TaxID=451804;
RN [1]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=CEA10 / CBS 144.89 / FGSC A1163;
RX PubMed=18404212; DOI=10.1371/journal.pgen.1000046;
RA Fedorova N.D., Khaldi N., Joardar V.S., Maiti R., Amedeo P., Anderson M.J.,
RA Crabtree J., Silva J.C., Badger J.H., Albarraq A., Angiuoli S., Bussey H.,
RA Bowyer P., Cotty P.J., Dyer P.S., Egan A., Galens K., Fraser-Liggett C.M.,
RA Haas B.J., Inman J.M., Kent R., Lemieux S., Malavazi I., Orvis J.,
RA Roemer T., Ronning C.M., Sundaram J.P., Sutton G., Turner G., Venter J.C.,
RA White O.R., Whitty B.R., Youngman P., Wolfe K.H., Goldman G.H.,
RA Wortman J.R., Jiang B., Denning D.W., Nierman W.C.;
RT "Genomic islands in the pathogenic filamentous fungus Aspergillus
RT fumigatus.";
RL PLoS Genet. 4:E1000046-E1000046(2008).
RN [2]
RP FUNCTION, CATALYTIC ACTIVITY, DISRUPTION PHENOTYPE, AND INDUCTION.
RC STRAIN=CEA10 / CBS 144.89 / FGSC A1163;
RX PubMed=17973657; DOI=10.1111/j.1462-5822.2007.1025.x;
RA Ibrahim-Granet O., Dubourdeau M., Latge J.P., Ave P., Huerre M.,
RA Brakhage A.A., Brock M.;
RT "Methylcitrate synthase from Aspergillus fumigatus is essential for
RT manifestation of invasive aspergillosis.";
RL Cell. Microbiol. 10:134-148(2008).
RN [3]
RP DISRUPTION PHENOTYPE.
RX PubMed=20421382; DOI=10.1128/iai.00268-10;
RA Jacobsen I.D., Grosse K., Slesiona S., Hube B., Berndt A., Brock M.;
RT "Embryonated eggs as an alternative infection model to investigate
RT Aspergillus fumigatus virulence.";
RL Infect. Immun. 78:2995-3006(2010).
CC -!- FUNCTION: Component of the methylcitrate cycle that catalyzes the
CC synthesis of (2S,3S)-2-methylcitrate from propionyl-CoA and
CC oxaloacetate. Plays an important role in detoxification of propionyl-
CC CoA, an inhibitor of both primary and secondary metabolism. Has also
CC citrate synthase activity using as substrates acetyl-CoA and
CC oxaloacetate. Plays a key role in the estabishment of invasive
CC pulmonary aspergillosis. {ECO:0000269|PubMed:17973657}.
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:17973657};
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;
CC Evidence={ECO:0000269|PubMed:17973657};
CC -!- PATHWAY: Organic acid metabolism; propanoate degradation.
CC {ECO:0000305}.
CC -!- SUBUNIT: Homodimer. {ECO:0000305}.
CC -!- SUBCELLULAR LOCATION: Mitochondrion matrix {ECO:0000305}.
CC -!- INDUCTION: Expression is induced by peptone and during infection.
CC {ECO:0000269|PubMed:17973657}.
CC -!- DISRUPTION PHENOTYPE: Leads to attenuated virulence in a mouse model
CC for pulmonary infection and an infection model based on embryonated
CC eggs. {ECO:0000269|PubMed:17973657, ECO:0000269|PubMed:20421382}.
CC -!- SIMILARITY: Belongs to the citrate synthase family. {ECO:0000305}.
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DR EMBL; DS499602; EDP47623.1; -; Genomic_DNA.
DR PDB; 6BOL; X-ray; 2.20 A; A/B=29-465.
DR PDB; 6BOM; X-ray; 2.05 A; A/B/C/D/E/F=29-465.
DR PDB; 6BON; X-ray; 2.35 A; A/B=29-465.
DR PDB; 6BOO; X-ray; 2.60 A; A/B/C/D=29-465.
DR PDBsum; 6BOL; -.
DR PDBsum; 6BOM; -.
DR PDBsum; 6BON; -.
DR PDBsum; 6BOO; -.
DR AlphaFoldDB; B0YD89; -.
DR SMR; B0YD89; -.
DR EnsemblFungi; EDP47623; EDP47623; AFUB_094700.
DR VEuPathDB; FungiDB:AFUB_094700; -.
DR HOGENOM; CLU_022049_2_1_1; -.
DR PhylomeDB; B0YD89; -.
DR UniPathway; UPA00946; -.
DR Proteomes; UP000001699; Unassembled WGS sequence.
DR GO; GO:0005759; C:mitochondrial matrix; IEA:UniProtKB-SubCell.
DR GO; GO:0050440; F:2-methylcitrate synthase activity; IEA:UniProtKB-EC.
DR GO; GO:0004108; F:citrate (Si)-synthase activity; IEA:EnsemblFungi.
DR GO; GO:0019629; P:propionate catabolic process, 2-methylcitrate cycle; IEA:EnsemblFungi.
DR GO; GO:0006099; P:tricarboxylic acid cycle; IEA:EnsemblFungi.
DR Gene3D; 1.10.230.10; -; 1.
DR Gene3D; 1.10.580.10; -; 1.
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; IPR036969; Citrate_synthase_sf.
DR PANTHER; PTHR11739; PTHR11739; 1.
DR Pfam; PF00285; Citrate_synt; 1.
DR PRINTS; PR00143; CITRTSNTHASE.
DR SUPFAM; SSF48256; SSF48256; 1.
DR PROSITE; PS00480; CITRATE_SYNTHASE; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Mitochondrion; Transferase; Transit peptide; Virulence.
FT TRANSIT 1..29
FT /note="Mitochondrion"
FT /evidence="ECO:0000255"
FT CHAIN 30..465
FT /note="2-methylcitrate synthase, mitochondrial"
FT /evidence="ECO:0000255"
FT /id="PRO_0000432972"
FT ACT_SITE 305
FT /evidence="ECO:0000250|UniProtKB:O34002"
FT ACT_SITE 351
FT /evidence="ECO:0000250|UniProtKB:O34002"
FT ACT_SITE 408
FT /evidence="ECO:0000250|UniProtKB:O34002"
FT BINDING 269
FT /ligand="substrate"
FT /evidence="ECO:0000250|UniProtKB:I6Y9Q3"
FT BINDING 345..349
FT /ligand="CoA"
FT /ligand_id="ChEBI:CHEBI:57287"
FT /evidence="ECO:0000250|UniProtKB:O34002"
FT BINDING 360
FT /ligand="substrate"
FT /evidence="ECO:0000250|UniProtKB:I6Y9Q3"
FT BINDING 434
FT /ligand="substrate"
FT /evidence="ECO:0000250|UniProtKB:I6Y9Q3"
FT HELIX 35..55
FT /evidence="ECO:0007829|PDB:6BOM"
FT TURN 56..58
FT /evidence="ECO:0007829|PDB:6BOM"
FT STRAND 60..65
FT /evidence="ECO:0007829|PDB:6BOM"
FT HELIX 66..70
FT /evidence="ECO:0007829|PDB:6BOM"
FT TURN 71..75
FT /evidence="ECO:0007829|PDB:6BOM"
FT STRAND 77..80
FT /evidence="ECO:0007829|PDB:6BOM"
FT STRAND 83..87
FT /evidence="ECO:0007829|PDB:6BOM"
FT TURN 88..90
FT /evidence="ECO:0007829|PDB:6BOM"
FT STRAND 91..94
FT /evidence="ECO:0007829|PDB:6BOM"
FT HELIX 99..105
FT /evidence="ECO:0007829|PDB:6BOM"
FT STRAND 110..115
FT /evidence="ECO:0007829|PDB:6BOM"
FT HELIX 117..126
FT /evidence="ECO:0007829|PDB:6BOM"
FT HELIX 132..144
FT /evidence="ECO:0007829|PDB:6BOM"
FT HELIX 150..158
FT /evidence="ECO:0007829|PDB:6BOM"
FT HELIX 165..175
FT /evidence="ECO:0007829|PDB:6BOM"
FT HELIX 176..179
FT /evidence="ECO:0007829|PDB:6BOM"
FT HELIX 181..188
FT /evidence="ECO:0007829|PDB:6BOM"
FT HELIX 192..194
FT /evidence="ECO:0007829|PDB:6BOM"
FT HELIX 196..218
FT /evidence="ECO:0007829|PDB:6BOM"
FT HELIX 220..222
FT /evidence="ECO:0007829|PDB:6BOM"
FT HELIX 223..228
FT /evidence="ECO:0007829|PDB:6BOM"
FT HELIX 237..244
FT /evidence="ECO:0007829|PDB:6BOM"
FT HELIX 250..252
FT /evidence="ECO:0007829|PDB:6BOM"
FT HELIX 253..265
FT /evidence="ECO:0007829|PDB:6BOM"
FT HELIX 274..284
FT /evidence="ECO:0007829|PDB:6BOM"
FT HELIX 289..300
FT /evidence="ECO:0007829|PDB:6BOM"
FT HELIX 303..306
FT /evidence="ECO:0007829|PDB:6BOM"
FT HELIX 308..323
FT /evidence="ECO:0007829|PDB:6BOM"
FT HELIX 329..341
FT /evidence="ECO:0007829|PDB:6BOM"
FT HELIX 359..369
FT /evidence="ECO:0007829|PDB:6BOM"
FT HELIX 372..375
FT /evidence="ECO:0007829|PDB:6BOM"
FT HELIX 378..397
FT /evidence="ECO:0007829|PDB:6BOM"
FT STRAND 400..402
FT /evidence="ECO:0007829|PDB:6BOM"
FT HELIX 407..409
FT /evidence="ECO:0007829|PDB:6BOM"
FT HELIX 411..417
FT /evidence="ECO:0007829|PDB:6BOM"
FT HELIX 423..425
FT /evidence="ECO:0007829|PDB:6BOM"
FT HELIX 426..433
FT /evidence="ECO:0007829|PDB:6BOM"
FT HELIX 436..448
FT /evidence="ECO:0007829|PDB:6BOM"
FT STRAND 456..458
FT /evidence="ECO:0007829|PDB:6BOM"
FT HELIX 460..464
FT /evidence="ECO:0007829|PDB:6BOM"
SQ SEQUENCE 465 AA; 51412 MW; B4A4C5903B04E125 CRC64;
MAMTMRSTRH ASKLAQTARL ALTNSRRYST AEPDLKTALK AVIPAKRELF KQVKERSDEV
IGEVKVANVI GGMRGLKSML WEGSVLDPEE GIRFHGKTIK DCQKELPKGT SGTEMLPEAM
FWLLLTGQVP STNQVRAFSR ELAEQSHLPQ HILDLIKSFP RSMHPMTQLS IAVAALNTES
KFAKAYEKGL SKADYWEPTF DDSISLLAKI PRVAALVFRP DEVDQVGTQA LDASQDWSYN
FAELLGKGGK ENQDFHDLLR LYLALHGDHE GGNVSAHATH LVGSALSDPF LSYSAGLLGL
AGPLHGLAAQ EVLRWILAMQ DKIGTKFTDD DVRNYLWDTL KSGRVVPGYG HGVLRKPDPR
FQALMDFAAT RPDVLANPVF QLVKKNSEIA PAVLTEHGKT KNPHPNVDAA SGVLFYHYGF
QQPLYYTVTF GVSRALGPLV QLIWDRALGL PIERPKSINL LGLKK
