PRPC_ASPFM
ID PRPC_ASPFM Reviewed; 465 AA.
AC Q50I20; Q4WD58;
DT 29-APR-2015, integrated into UniProtKB/Swiss-Prot.
DT 07-JUN-2005, sequence version 1.
DT 03-AUG-2022, entry version 94.
DE RecName: Full=2-methylcitrate synthase, mitochondrial {ECO:0000305};
DE Short=Methylcitrate synthase {ECO:0000303|PubMed:16008561};
DE EC=2.3.3.5 {ECO:0000269|PubMed:16008561};
DE AltName: Full=(2S,3S)-2-methylcitrate synthase {ECO:0000250|UniProtKB:P31660};
DE AltName: Full=Citrate synthase 1 {ECO:0000305};
DE EC=2.3.3.16 {ECO:0000269|PubMed:16008561};
DE Flags: Precursor;
GN Name=mcsA {ECO:0000303|PubMed:16008561};
GN Synonyms=cit1 {ECO:0000303|PubMed:20507060};
OS Neosartorya fumigata (Aspergillus fumigatus).
OC Eukaryota; Fungi; Dikarya; Ascomycota; Pezizomycotina; Eurotiomycetes;
OC Eurotiomycetidae; Eurotiales; Aspergillaceae; Aspergillus;
OC Aspergillus subgen. Fumigati.
OX NCBI_TaxID=746128 {ECO:0000312|EMBL:CAI61947.1};
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA], PROTEIN SEQUENCE OF 34-55, TRANSIT PEPTIDE,
RP FUNCTION, CATALYTIC ACTIVITY, BIOPHYSICOCHEMICAL PROPERTIES, AND DISRUPTION
RP PHENOTYPE.
RC STRAIN=ATCC 46645 / NCPF 2109;
RX PubMed=16008561; DOI=10.1111/j.1742-4658.2005.04784.x;
RA Maerker C., Rohde M., Brakhage A.A., Brock M.;
RT "Methylcitrate synthase from Aspergillus fumigatus. Propionyl-CoA affects
RT polyketide synthesis, growth and morphology of conidia.";
RL FEBS J. 272:3615-3630(2005).
RN [2]
RP IDENTIFICATION BY MASS SPECTROMETRY, AND DEVELOPMENTAL STAGE.
RC STRAIN=ATCC 46645 / NCPF 2109;
RX PubMed=20507060; DOI=10.1021/pr9010684;
RA Teutschbein J., Albrecht D., Potsch M., Guthke R., Aimanianda V.,
RA Clavaud C., Latge J.P., Brakhage A.A., Kniemeyer O.;
RT "Proteome profiling and functional classification of intracellular proteins
RT from conidia of the human-pathogenic mold Aspergillus fumigatus.";
RL J. Proteome Res. 9:3427-3442(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. May play a role in virulence.
CC {ECO:0000269|PubMed:16008561}.
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:16008561};
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:16008561};
CC -!- BIOPHYSICOCHEMICAL PROPERTIES:
CC Kinetic parameters:
CC KM=1.9 uM for propionyl-CoA {ECO:0000269|PubMed:16008561};
CC KM=2.6 uM for acetyl-CoA {ECO:0000269|PubMed:16008561};
CC KM=2.7 uM for oxaloacetate {ECO:0000269|PubMed:16008561};
CC pH dependence:
CC Optimum pH is 8.0-9.0. {ECO:0000269|PubMed:16008561};
CC Temperature dependence:
CC Optimum temperature is 50-60 degrees Celsius.
CC {ECO:0000269|PubMed:16008561};
CC -!- PATHWAY: Organic acid metabolism; propanoate degradation.
CC {ECO:0000305}.
CC -!- SUBUNIT: Homodimer. {ECO:0000305}.
CC -!- SUBCELLULAR LOCATION: Mitochondrion matrix {ECO:0000305}.
CC -!- DEVELOPMENTAL STAGE: Highly expressed in conidia.
CC {ECO:0000269|PubMed:20507060}.
CC -!- DISRUPTION PHENOTYPE: Leads to the inability to grow on propionate as
CC the sole carbon source, a strong reduction of growth rate and spore
CC color formation on media containing both glucose and propionate, and an
CC accumulation of propionyl-CoA. Leads also to an attenuation of
CC virulence in an insect infection model. {ECO:0000269|PubMed:16008561}.
CC -!- SIMILARITY: Belongs to the citrate synthase family. {ECO:0000305}.
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DR EMBL; AJ888885; CAI61947.1; -; mRNA.
DR PDB; 5UQO; X-ray; 2.50 A; A/B=29-465.
DR PDB; 5UQQ; X-ray; 2.30 A; A/B/C/D/E/F=29-465.
DR PDB; 5UQR; X-ray; 1.75 A; A/B=29-465.
DR PDB; 5UQU; X-ray; 1.70 A; A/B=29-465.
DR PDB; 6BOP; X-ray; 2.71 A; A/B/C/D=29-465.
DR PDBsum; 5UQO; -.
DR PDBsum; 5UQQ; -.
DR PDBsum; 5UQR; -.
DR PDBsum; 5UQU; -.
DR PDBsum; 6BOP; -.
DR AlphaFoldDB; Q50I20; -.
DR SMR; Q50I20; -.
DR OMA; AEYWEPT; -.
DR BRENDA; 2.3.3.5; 508.
DR UniPathway; UPA00946; -.
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:0036440; F:citrate synthase activity; IEA:UniProtKB-EC.
DR GO; GO:0019543; P:propionate catabolic process; IMP:AspGD.
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; Acyltransferase; Direct protein sequencing; Mitochondrion;
KW Transferase; Transit peptide.
FT TRANSIT 1..28
FT /note="Mitochondrion"
FT /evidence="ECO:0000269|PubMed:16008561"
FT CHAIN 29..465
FT /note="2-methylcitrate synthase, mitochondrial"
FT /evidence="ECO:0000255"
FT /id="PRO_5000074390"
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..54
FT /evidence="ECO:0007829|PDB:5UQU"
FT TURN 55..58
FT /evidence="ECO:0007829|PDB:5UQU"
FT STRAND 60..65
FT /evidence="ECO:0007829|PDB:5UQU"
FT HELIX 66..70
FT /evidence="ECO:0007829|PDB:5UQU"
FT TURN 71..75
FT /evidence="ECO:0007829|PDB:5UQU"
FT STRAND 77..80
FT /evidence="ECO:0007829|PDB:5UQU"
FT STRAND 83..87
FT /evidence="ECO:0007829|PDB:5UQU"
FT TURN 88..90
FT /evidence="ECO:0007829|PDB:5UQU"
FT STRAND 91..94
FT /evidence="ECO:0007829|PDB:5UQU"
FT HELIX 99..105
FT /evidence="ECO:0007829|PDB:5UQU"
FT STRAND 110..115
FT /evidence="ECO:0007829|PDB:5UQU"
FT HELIX 117..126
FT /evidence="ECO:0007829|PDB:5UQU"
FT HELIX 132..144
FT /evidence="ECO:0007829|PDB:5UQU"
FT HELIX 150..157
FT /evidence="ECO:0007829|PDB:5UQU"
FT HELIX 165..175
FT /evidence="ECO:0007829|PDB:5UQU"
FT HELIX 176..179
FT /evidence="ECO:0007829|PDB:5UQU"
FT HELIX 181..188
FT /evidence="ECO:0007829|PDB:5UQU"
FT HELIX 192..194
FT /evidence="ECO:0007829|PDB:5UQU"
FT HELIX 196..218
FT /evidence="ECO:0007829|PDB:5UQU"
FT HELIX 220..222
FT /evidence="ECO:0007829|PDB:5UQU"
FT HELIX 223..228
FT /evidence="ECO:0007829|PDB:5UQU"
FT HELIX 237..244
FT /evidence="ECO:0007829|PDB:5UQU"
FT HELIX 250..252
FT /evidence="ECO:0007829|PDB:5UQU"
FT HELIX 253..265
FT /evidence="ECO:0007829|PDB:5UQU"
FT HELIX 274..284
FT /evidence="ECO:0007829|PDB:5UQU"
FT HELIX 289..300
FT /evidence="ECO:0007829|PDB:5UQU"
FT TURN 303..307
FT /evidence="ECO:0007829|PDB:5UQU"
FT HELIX 308..323
FT /evidence="ECO:0007829|PDB:5UQU"
FT HELIX 329..341
FT /evidence="ECO:0007829|PDB:5UQU"
FT HELIX 359..369
FT /evidence="ECO:0007829|PDB:5UQU"
FT HELIX 372..375
FT /evidence="ECO:0007829|PDB:5UQU"
FT HELIX 378..397
FT /evidence="ECO:0007829|PDB:5UQU"
FT STRAND 400..402
FT /evidence="ECO:0007829|PDB:5UQU"
FT HELIX 408..417
FT /evidence="ECO:0007829|PDB:5UQU"
FT HELIX 423..425
FT /evidence="ECO:0007829|PDB:5UQR"
FT HELIX 426..433
FT /evidence="ECO:0007829|PDB:5UQU"
FT HELIX 436..448
FT /evidence="ECO:0007829|PDB:5UQU"
FT STRAND 456..458
FT /evidence="ECO:0007829|PDB:5UQU"
FT HELIX 460..464
FT /evidence="ECO:0007829|PDB:5UQU"
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
