ILVC_ASPFU
ID ILVC_ASPFU Reviewed; 606 AA.
AC Q4X099;
DT 29-SEP-2021, integrated into UniProtKB/Swiss-Prot.
DT 17-APR-2007, sequence version 2.
DT 03-AUG-2022, entry version 87.
DE RecName: Full=Dihydroxy-acid dehydratase ilvC, mitochondrial {ECO:0000303|PubMed:23028460};
DE Short=DHAD ilvC {ECO:0000303|PubMed:23028460};
DE EC=4.2.1.9 {ECO:0000250|UniProtKB:P39522};
GN Name=ilvC {ECO:0000303|PubMed:23028460};
GN Synonyms=ilv3A {ECO:0000303|PubMed:23028460}; ORFNames=AFUA_2G14210;
OS Neosartorya fumigata (strain ATCC MYA-4609 / Af293 / CBS 101355 / FGSC
OS A1100) (Aspergillus fumigatus).
OC Eukaryota; Fungi; Dikarya; Ascomycota; Pezizomycotina; Eurotiomycetes;
OC Eurotiomycetidae; Eurotiales; Aspergillaceae; Aspergillus;
OC Aspergillus subgen. Fumigati.
OX NCBI_TaxID=330879;
RN [1]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=ATCC MYA-4609 / Af293 / CBS 101355 / FGSC A1100;
RX PubMed=16372009; DOI=10.1038/nature04332;
RA Nierman W.C., Pain A., Anderson M.J., Wortman J.R., Kim H.S., Arroyo J.,
RA Berriman M., Abe K., Archer D.B., Bermejo C., Bennett J.W., Bowyer P.,
RA Chen D., Collins M., Coulsen R., Davies R., Dyer P.S., Farman M.L.,
RA Fedorova N., Fedorova N.D., Feldblyum T.V., Fischer R., Fosker N.,
RA Fraser A., Garcia J.L., Garcia M.J., Goble A., Goldman G.H., Gomi K.,
RA Griffith-Jones S., Gwilliam R., Haas B.J., Haas H., Harris D.E.,
RA Horiuchi H., Huang J., Humphray S., Jimenez J., Keller N., Khouri H.,
RA Kitamoto K., Kobayashi T., Konzack S., Kulkarni R., Kumagai T., Lafton A.,
RA Latge J.-P., Li W., Lord A., Lu C., Majoros W.H., May G.S., Miller B.L.,
RA Mohamoud Y., Molina M., Monod M., Mouyna I., Mulligan S., Murphy L.D.,
RA O'Neil S., Paulsen I., Penalva M.A., Pertea M., Price C., Pritchard B.L.,
RA Quail M.A., Rabbinowitsch E., Rawlins N., Rajandream M.A., Reichard U.,
RA Renauld H., Robson G.D., Rodriguez de Cordoba S., Rodriguez-Pena J.M.,
RA Ronning C.M., Rutter S., Salzberg S.L., Sanchez M., Sanchez-Ferrero J.C.,
RA Saunders D., Seeger K., Squares R., Squares S., Takeuchi M., Tekaia F.,
RA Turner G., Vazquez de Aldana C.R., Weidman J., White O., Woodward J.R.,
RA Yu J.-H., Fraser C.M., Galagan J.E., Asai K., Machida M., Hall N.,
RA Barrell B.G., Denning D.W.;
RT "Genomic sequence of the pathogenic and allergenic filamentous fungus
RT Aspergillus fumigatus.";
RL Nature 438:1151-1156(2005).
RN [2]
RP FUNCTION, DISRUPTION PHENOTYPE, BIOPHYSICOCHEMICAL PROPERTIES, ACTIVITY
RP REGULATION, AND PATHWAY.
RX PubMed=23028460; DOI=10.1371/journal.pone.0043559;
RA Oliver J.D., Kaye S.J., Tuckwell D., Johns A.E., Macdonald D.A.,
RA Livermore J., Warn P.A., Birch M., Bromley M.J.;
RT "The Aspergillus fumigatus dihydroxyacid dehydratase Ilv3A/IlvC is required
RT for full virulence.";
RL PLoS ONE 7:e43559-e43559(2012).
CC -!- FUNCTION: Dihydroxyacid dehydratase that catalyzes the third step in
CC the common pathway leading to biosynthesis of branched-chain amino
CC acids (PubMed:23028460). Catalyzes the dehydration of (2R,3R)-2,3-
CC dihydroxy-3-methylpentanoate (2,3-dihydroxy-3-methylvalerate) into 2-
CC oxo-3-methylpentanoate (2-oxo-3-methylvalerate) and of (2R)-2,3-
CC dihydroxy-3-methylbutanoate (2,3-dihydroxyisovalerate) into 2-oxo-3-
CC methylbutanoate (2-oxoisovalerate), the penultimate precursor to L-
CC isoleucine and L-valine, respectively (By similarity). IlvC and the
CC branched-chain amino acid biosynthesis are crucial for virulence and
CC may be a potential target to develop antifungal agents
CC (PubMed:23028460). {ECO:0000250|UniProtKB:P39522,
CC ECO:0000269|PubMed:23028460}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=(2R)-2,3-dihydroxy-3-methylbutanoate = 3-methyl-2-oxobutanoate
CC + H2O; Xref=Rhea:RHEA:24809, ChEBI:CHEBI:11851, ChEBI:CHEBI:15377,
CC ChEBI:CHEBI:49072; EC=4.2.1.9;
CC Evidence={ECO:0000250|UniProtKB:P39522};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:24810;
CC Evidence={ECO:0000250|UniProtKB:P39522};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=(2R,3R)-2,3-dihydroxy-3-methylpentanoate = (S)-3-methyl-2-
CC oxopentanoate + H2O; Xref=Rhea:RHEA:27694, ChEBI:CHEBI:15377,
CC ChEBI:CHEBI:35146, ChEBI:CHEBI:49258; EC=4.2.1.9;
CC Evidence={ECO:0000250|UniProtKB:P05791};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:27695;
CC Evidence={ECO:0000250|UniProtKB:P05791};
CC -!- COFACTOR:
CC Name=[2Fe-2S] cluster; Xref=ChEBI:CHEBI:190135;
CC Evidence={ECO:0000250|UniProtKB:P39522};
CC Note=Binds 1 [2Fe-2S] cluster per subunit.
CC {ECO:0000250|UniProtKB:P39522};
CC -!- COFACTOR:
CC Name=Mg(2+); Xref=ChEBI:CHEBI:18420;
CC Evidence={ECO:0000250|UniProtKB:P9WKJ5};
CC -!- ACTIVITY REGULATION: DHAD activity is inhibited in dose-dependent
CC manner by 2-hydroxy-3-methylbutyric acid with an IC(50) of about 8 mM.
CC {ECO:0000269|PubMed:23028460}.
CC -!- BIOPHYSICOCHEMICAL PROPERTIES:
CC Kinetic parameters:
CC KM=10.1 mM for L-threonate {ECO:0000269|PubMed:23028460};
CC Vmax=18 umol/min/mg enzyme using the non-natural substrate L-
CC threonate {ECO:0000269|PubMed:23028460};
CC -!- PATHWAY: Amino-acid biosynthesis; L-isoleucine biosynthesis; L-
CC isoleucine from 2-oxobutanoate: step 3/4.
CC {ECO:0000269|PubMed:23028460}.
CC -!- PATHWAY: Amino-acid biosynthesis; L-valine biosynthesis; L-valine from
CC pyruvate: step 3/4. {ECO:0000269|PubMed:23028460}.
CC -!- SUBCELLULAR LOCATION: Mitochondrion {ECO:0000250|UniProtKB:P39522}.
CC -!- DISRUPTION PHENOTYPE: Requires supplementation with isoleucine and
CC valine for growth (PubMed:23028460). Results in considerably lower
CC kidney tissue burden in murine infection models (PubMed:23028460).
CC {ECO:0000269|PubMed:23028460}.
CC -!- SIMILARITY: Belongs to the IlvD/Edd family. {ECO:0000305}.
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DR EMBL; AAHF01000001; EAL93716.2; -; Genomic_DNA.
DR RefSeq; XP_755754.2; XM_750661.2.
DR SMR; Q4X099; -.
DR STRING; 746128.CADAFUBP00002922; -.
DR SwissPalm; Q4X099; -.
DR EnsemblFungi; EAL93716; EAL93716; AFUA_2G14210.
DR GeneID; 3512998; -.
DR KEGG; afm:AFUA_2G14210; -.
DR VEuPathDB; FungiDB:Afu2g14210; -.
DR eggNOG; KOG2448; Eukaryota.
DR HOGENOM; CLU_014271_4_2_1; -.
DR InParanoid; Q4X099; -.
DR OMA; TQGRNMA; -.
DR OrthoDB; 500676at2759; -.
DR UniPathway; UPA00047; UER00057.
DR UniPathway; UPA00049; UER00061.
DR PHI-base; PHI:2638; -.
DR Proteomes; UP000002530; Chromosome 2.
DR GO; GO:0005739; C:mitochondrion; IEA:UniProtKB-SubCell.
DR GO; GO:0051537; F:2 iron, 2 sulfur cluster binding; IEA:UniProtKB-KW.
DR GO; GO:0004160; F:dihydroxy-acid dehydratase activity; IDA:AspGD.
DR GO; GO:0046872; F:metal ion binding; IEA:UniProtKB-KW.
DR GO; GO:0009082; P:branched-chain amino acid biosynthetic process; IMP:AspGD.
DR GO; GO:0009097; P:isoleucine biosynthetic process; IEA:UniProtKB-UniPathway.
DR GO; GO:0009099; P:valine biosynthetic process; IEA:UniProtKB-UniPathway.
DR Gene3D; 3.50.30.80; -; 1.
DR HAMAP; MF_00012; IlvD; 1.
DR InterPro; IPR042096; Dihydro-acid_dehy_C.
DR InterPro; IPR004404; DihydroxyA_deHydtase.
DR InterPro; IPR000581; DiOHA_6PGluconate_deHydtase.
DR InterPro; IPR020558; DiOHA_6PGluconate_deHydtase_CS.
DR InterPro; IPR037237; IlvD/EDD_N.
DR Pfam; PF00920; ILVD_EDD; 1.
DR SUPFAM; SSF143975; SSF143975; 1.
DR TIGRFAMs; TIGR00110; ilvD; 1.
DR PROSITE; PS00886; ILVD_EDD_1; 1.
DR PROSITE; PS00887; ILVD_EDD_2; 1.
PE 1: Evidence at protein level;
KW 2Fe-2S; Amino-acid biosynthesis; Branched-chain amino acid biosynthesis;
KW Iron; Iron-sulfur; Lyase; Magnesium; Metal-binding; Mitochondrion;
KW Reference proteome; Virulence.
FT CHAIN 1..606
FT /note="Dihydroxy-acid dehydratase ilvC, mitochondrial"
FT /id="PRO_0000453258"
FT ACT_SITE 511
FT /note="Proton acceptor"
FT /evidence="ECO:0000250|UniProtKB:P9WKJ5"
FT BINDING 84
FT /ligand="[2Fe-2S] cluster"
FT /ligand_id="ChEBI:CHEBI:190135"
FT /evidence="ECO:0000250|UniProtKB:P9WKJ5"
FT BINDING 116
FT /ligand="Mg(2+)"
FT /ligand_id="ChEBI:CHEBI:18420"
FT /evidence="ECO:0000250|UniProtKB:P9WKJ5"
FT BINDING 157
FT /ligand="[2Fe-2S] cluster"
FT /ligand_id="ChEBI:CHEBI:190135"
FT /evidence="ECO:0000250|UniProtKB:P9WKJ5"
FT BINDING 158
FT /ligand="Mg(2+)"
FT /ligand_id="ChEBI:CHEBI:18420"
FT /evidence="ECO:0000250|UniProtKB:P9WKJ5"
FT BINDING 232
FT /ligand="[2Fe-2S] cluster"
FT /ligand_id="ChEBI:CHEBI:190135"
FT /evidence="ECO:0000250|UniProtKB:P9WKJ5"
FT BINDING 485
FT /ligand="Mg(2+)"
FT /ligand_id="ChEBI:CHEBI:18420"
FT /evidence="ECO:0000250|UniProtKB:P9WKJ5"
SQ SEQUENCE 606 AA; 64757 MW; 3D97EDCABF49E1DF CRC64;
MLLSQTRGRL PSTLRSFSRR ALSTTLPRGK DSEETALNKV SRNVTQPISQ GASQAMLYAT
GLTEEDMNKA QVGISSVWYN GNPCNMHLLD LSNRVREGVQ KAGLVGFQFN TVGVSDAISM
GTKGMRYSLQ SRDLIADSIE TVMGGQWYDA NISIPGCDKN MPGVLMAMGR VNRPSLMVYG
GTIKPGCART QNNADIDIVS AFQAYGQFLT GEITENQRFD IIRNACPGGG ACGGMYTANT
MATAIEVMGM TLPGSSSNPA ESKAKDLECL AAGEAIKRLL KEDIRPSDIL TRQAFENAMI
VVNITGGSTN AVLHLIAIAD SVGIKLDIED FQKVSDRTPF LADLKPSGKY VMADLHNIGG
TPSLLKFLLK EGVIDGSGMT VTGETLAKNL EKVPDFPADQ KIIRPLSNPI KKTGHIQILR
GSLAPGGSVG KITGKEGTRF VGKARVFDDE DDFIAALERN EIKKEEKTVV VIRYTGPKGG
PGMPEMLKPS SALMGAGLGS SCALITDGRF SGGSHGFLIG HIVPEAAVGG PIGLVKDGDT
ITIDAEKRLL DLDVDETELA RRRKEWEALR DAGKLPQTGL TMRGTLGKYA RTVKDASHGC
ITDSVE
