HTYC_ASPRU
ID HTYC_ASPRU Reviewed; 366 AA.
AC K0E689;
DT 25-APR-2018, integrated into UniProtKB/Swiss-Prot.
DT 28-NOV-2012, sequence version 1.
DT 03-AUG-2022, entry version 32.
DE RecName: Full=Isopropyl malate dehydrogenase htyC {ECO:0000303|PubMed:22998630};
DE EC=1.1.1.85 {ECO:0000305|PubMed:22998630};
DE AltName: Full=L-homotyrosine biosynthetic cluster protein C {ECO:0000303|PubMed:22998630};
GN Name=htyC {ECO:0000303|PubMed:22998630};
OS Aspergillus rugulosus (Emericella rugulosa).
OC Eukaryota; Fungi; Dikarya; Ascomycota; Pezizomycotina; Eurotiomycetes;
OC Eurotiomycetidae; Eurotiales; Aspergillaceae; Aspergillus.
OX NCBI_TaxID=41736;
RN [1]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA], FUNCTION, PATHWAY, AND BIOTECHNOLOGY.
RC STRAIN=ATCC 58397 / NRRL 11440;
RX PubMed=22998630; DOI=10.1021/ja307220z;
RA Cacho R.A., Jiang W., Chooi Y.H., Walsh C.T., Tang Y.;
RT "Identification and characterization of the echinocandin B biosynthetic
RT gene cluster from Emericella rugulosa NRRL 11440.";
RL J. Am. Chem. Soc. 134:16781-16790(2012).
CC -!- FUNCTION: Isopropyl malate dehydrogenase; part of the gene cluster that
CC mediates the de novo generation of L-homotyrosine from acetyl-CoA and
CC 4-hydroxyphenyl-pyruvate (PubMed:22998630). L-homotyrosine is a
CC building block of echinocandin B, a fungal lipidated cyclic hexapeptide
CC that acts as an antifungal agent (PubMed:22998630). L-homotyrosine 4-
CC hydroxyphenyl-pyruvate first undergoes an aldol-type condensation by
CC htyA with the C-2 of acetyl-CoA followed by the release of CoA to form
CC 2-(4-hydroxybenzyl)-malate (PubMed:22998630). This is followed by
CC isomerization of 2-(4-hydroxy-benzyl)-malate to 3-(4-hydroxybenzyl)-
CC malate by htyD (PubMed:22998630). Thereafter, 3-(4-hydroxybenzyl)-
CC malate undergoes decarboxylation and oxidation to form 2-oxo-4-(4-
CC hydroxybenzyl)butanoic acid, coupled to reduction of NAD(+) to NADH by
CC htyC (PubMed:22998630). The product then undergoes transamination
CC catalyzed by htyB to form L-homotyrosine (PubMed:22998630).
CC {ECO:0000269|PubMed:22998630}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=(2R,3S)-3-isopropylmalate + NAD(+) = 4-methyl-2-oxopentanoate
CC + CO2 + NADH; Xref=Rhea:RHEA:32271, ChEBI:CHEBI:16526,
CC ChEBI:CHEBI:17865, ChEBI:CHEBI:35121, ChEBI:CHEBI:57540,
CC ChEBI:CHEBI:57945; EC=1.1.1.85;
CC Evidence={ECO:0000255|RuleBase:RU004445};
CC -!- COFACTOR:
CC Name=Mg(2+); Xref=ChEBI:CHEBI:18420;
CC Evidence={ECO:0000255|RuleBase:RU004445};
CC Name=Mn(2+); Xref=ChEBI:CHEBI:29035;
CC Evidence={ECO:0000255|RuleBase:RU004445};
CC Note=Binds 1 Mg(2+) or Mn(2+) ion per subunit.
CC {ECO:0000255|RuleBase:RU004445};
CC -!- PATHWAY: Antifungal biosynthesis. {ECO:0000305|PubMed:22998630}.
CC -!- SUBUNIT: Homodimer. {ECO:0000255|RuleBase:RU004445}.
CC -!- BIOTECHNOLOGY: Due to their effectiveness as antifungal agents,
CC echinocandin derivatives can be used for the treatment of human
CC invasive candidiasis (PubMed:22998630). {ECO:0000269|PubMed:22998630}.
CC -!- SIMILARITY: Belongs to the isocitrate and isopropylmalate
CC dehydrogenases family. {ECO:0000305}.
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DR EMBL; JX421685; AFT91394.1; -; Genomic_DNA.
DR AlphaFoldDB; K0E689; -.
DR SMR; K0E689; -.
DR BioCyc; MetaCyc:MON-19236; -.
DR GO; GO:0003862; F:3-isopropylmalate dehydrogenase activity; IEA:UniProtKB-EC.
DR GO; GO:0000287; F:magnesium ion binding; IEA:InterPro.
DR GO; GO:0051287; F:NAD binding; IEA:InterPro.
DR GO; GO:0009098; P:leucine biosynthetic process; IEA:UniProtKB-KW.
DR InterPro; IPR019818; IsoCit/isopropylmalate_DH_CS.
DR InterPro; IPR024084; IsoPropMal-DH-like_dom.
DR InterPro; IPR004429; Isopropylmalate_DH.
DR PANTHER; PTHR42979; PTHR42979; 1.
DR Pfam; PF00180; Iso_dh; 1.
DR SMART; SM01329; Iso_dh; 1.
DR TIGRFAMs; TIGR00169; leuB; 1.
DR PROSITE; PS00470; IDH_IMDH; 1.
PE 1: Evidence at protein level;
KW Amino-acid biosynthesis; Branched-chain amino acid biosynthesis;
KW Leucine biosynthesis; Magnesium; Manganese; Metal-binding; NAD; NADP;
KW Oxidoreductase.
FT CHAIN 1..366
FT /note="Isopropyl malate dehydrogenase htyC"
FT /id="PRO_0000443853"
FT BINDING 71..73
FT /ligand="NADP(+)"
FT /ligand_id="ChEBI:CHEBI:58349"
FT /evidence="ECO:0000250|UniProtKB:O75874"
FT BINDING 91
FT /ligand="substrate"
FT /evidence="ECO:0000250|UniProtKB:O75874"
FT BINDING 130
FT /ligand="substrate"
FT /evidence="ECO:0000250|UniProtKB:P50213"
FT BINDING 221
FT /ligand="Mg(2+)"
FT /ligand_id="ChEBI:CHEBI:18420"
FT /evidence="ECO:0000250|UniProtKB:P50213"
FT BINDING 246
FT /ligand="Mg(2+)"
FT /ligand_id="ChEBI:CHEBI:18420"
FT /evidence="ECO:0000250|UniProtKB:P50213"
FT BINDING 250
FT /ligand="Mg(2+)"
FT /ligand_id="ChEBI:CHEBI:18420"
FT /evidence="ECO:0000250|UniProtKB:P50213"
FT BINDING 277..282
FT /ligand="NADP(+)"
FT /ligand_id="ChEBI:CHEBI:58349"
FT /evidence="ECO:0000250|UniProtKB:O75874"
FT SITE 137
FT /note="Critical for catalysis"
FT /evidence="ECO:0000250|UniProtKB:P50213"
FT SITE 187
FT /note="Critical for catalysis"
FT /evidence="ECO:0000250|UniProtKB:P50213"
SQ SEQUENCE 366 AA; 38706 MW; E1F25BB2C882E8A6 CRC64;
MVKTFDIVVF PGDYGGPEVL GEIQSQYEQE VTFNLKYHLL GGASFDAHGT PIADEALTDA
KAASAVLLGA VGGPAWDKAP IPVESGLGRL RKALDAFGNL RPVKFIHPIL TETSALKEQV
CRGADLLIIR ELTGGIYYGA RQEHDGTLNA ASDLDHYERA QVQRVARLAG TLAMSTQPPT
PITSLDKANL LAACGRLWRG VVEETIRREF PDVELKHMLI DTAAMTLGCR PTKLNGIVLT
SNMFGDIISD QASAIPGSLG LLPSASLCAI PGGESGGCVH GIYEPVHGSA PDIAGQGIIN
PTGMILSVAM MLRYSLDMPA AATAVETAVS RVIERGGRTR DVGGTTSTAE FGDQVVACLR
ENTEDK
