AMT6_ALTAL
ID AMT6_ALTAL Reviewed; 373 AA.
AC C9K7B7;
DT 18-JUL-2018, integrated into UniProtKB/Swiss-Prot.
DT 24-NOV-2009, sequence version 1.
DT 03-AUG-2022, entry version 60.
DE RecName: Full=3-isopropylmalate dehydrogenase AMT6 {ECO:0000250|UniProtKB:K0E689};
DE EC=1.1.1.85 {ECO:0000255|RuleBase:RU004445};
DE AltName: Full=AM-toxin biosynthesis protein 6 {ECO:0000303|PubMed:17990954};
GN Name=AMT6 {ECO:0000303|PubMed:17990954};
OS Alternaria alternata (Alternaria rot fungus) (Torula alternata).
OC Eukaryota; Fungi; Dikarya; Ascomycota; Pezizomycotina; Dothideomycetes;
OC Pleosporomycetidae; Pleosporales; Pleosporineae; Pleosporaceae; Alternaria;
OC Alternaria sect. Alternaria; Alternaria alternata complex.
OX NCBI_TaxID=5599;
RN [1]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA], INDUCTION, AND PATHWAY.
RC STRAIN=NBRC 8984;
RX PubMed=17990954; DOI=10.1094/mpmi-20-12-1463;
RA Harimoto Y., Hatta R., Kodama M., Yamamoto M., Otani H., Tsuge T.;
RT "Expression profiles of genes encoded by the supernumerary chromosome
RT controlling AM-toxin biosynthesis and pathogenicity in the apple pathotype
RT of Alternaria alternata.";
RL Mol. Plant Microbe Interact. 20:1463-1476(2007).
RN [2]
RP FUNCTION.
RC STRAIN=M-71;
RX PubMed=10875335; DOI=10.1094/mpmi.2000.13.7.742;
RA Johnson R.D., Johnson L., Itoh Y., Kodama M., Otani H., Kohmoto K.;
RT "Cloning and characterization of a cyclic peptide synthetase gene from
RT Alternaria alternata apple pathotype whose product is involved in AM-toxin
RT synthesis and pathogenicity.";
RL Mol. Plant Microbe Interact. 13:742-753(2000).
RN [3]
RP FUNCTION.
RC STRAIN=NBRC 8984;
RX PubMed=15066029; DOI=10.1111/j.1365-2958.2004.04004.x;
RA Ito K., Tanaka T., Hatta R., Yamamoto M., Akimitsu K., Tsuge T.;
RT "Dissection of the host range of the fungal plant pathogen Alternaria
RT alternata by modification of secondary metabolism.";
RL Mol. Microbiol. 52:399-411(2004).
RN [4]
RP REVIEW ON HOST-SELECTIVE TOXINS.
RX PubMed=22846083; DOI=10.1111/j.1574-6976.2012.00350.x;
RA Tsuge T., Harimoto Y., Akimitsu K., Ohtani K., Kodama M., Akagi Y.,
RA Egusa M., Yamamoto M., Otani H.;
RT "Host-selective toxins produced by the plant pathogenic fungus Alternaria
RT alternata.";
RL FEMS Microbiol. Rev. 37:44-66(2013).
CC -!- FUNCTION: 3-isopropylmalate dehydrogenase; part of the gene clusters
CC that mediate the biosynthesis of AM-toxins, host-selective toxins
CC (HSTs) causing Alternaria blotch on apple, a worldwide distributed
CC disease (Probable). AM-toxins are cyclic depsipeptides containing the 3
CC residues 2-hydroxy-isovaleric acid (2-HIV), dehydroalanine, L-alanine
CC which are common for all 3 AM-toxins I to III. The fourth precursor is
CC L-alpha-amino-methoxyphenyl-valeric acid (L-Amv) for AM-toxin I, L-
CC alpha-amino-phenyl-valeric acid (L-Apv) for AM-toxin II, and L-alpha-
CC amino-hydroxyphenyl-valeric acid (L-Ahv) for AM-toxin III (Probable).
CC AM-toxins have two target sites for affecting susceptible apple cells;
CC they cause invagination of the plasma membrane and electrolyte loss and
CC chloroplast disorganization (PubMed:22846083). The non-ribosomal
CC peptide synthetase AMT1 contains 4 catalytic modules and is responsible
CC for activation of each residue in AM-toxin (PubMed:10875335). The aldo-
CC keto reductase AMT2 catalyzes the conversion of 2-keto-isovaleric acid
CC (2-KIV) to 2-hydroxy-isovaleric acid (2-HIV), one of the precursor
CC residues incorporated by AMT1 during AM-toxin biosynthesis, by
CC reduction of its ketone to an alcohol (PubMed:15066029). The cytochrome
CC P450 monooxygenase AMT3 and the thioesterase AMT4 are also important
CC for AM-toxin production, but their exact function within the AM-toxin
CC biosynthesis are not known yet (PubMed:17990954). Up to 21 proteins
CC (including AMT1 to AMT4) are predicted to be involved in AM-toxin
CC biosynthesis since their expression ishighly up-regulated in AM-toxin-
CC producing cultures (PubMed:17990954). {ECO:0000269|PubMed:10875335,
CC ECO:0000269|PubMed:15066029, ECO:0000269|PubMed:17990954,
CC ECO:0000303|PubMed:22846083, ECO:0000305|PubMed:10875335,
CC ECO:0000305|PubMed:17990954}.
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: Amino-acid biosynthesis; L-leucine biosynthesis; L-leucine
CC from 3-methyl-2-oxobutanoate: step 3/4.
CC {ECO:0000255|RuleBase:RU004445}.
CC -!- PATHWAY: Mycotoxin biosynthesis. {ECO:0000305|PubMed:17990954}.
CC -!- SUBUNIT: Homodimer. {ECO:0000255|RuleBase:RU004445}.
CC -!- INDUCTION: Expression is up-regulated more than 10 fold in toxin
CC producing cultures. {ECO:0000269|PubMed:17990954}.
CC -!- MISCELLANEOUS: Gene clusters encoding host-selective toxins (HSTs) are
CC localized on conditionally dispensable chromosomes (CDCs), also called
CC supernumerary chromosomes, where they are present in multiple copies
CC (PubMed:17990954). The CDCs are not essential for saprophytic growth
CC but controls host-selective pathogenicity (PubMed:17990954).
CC {ECO:0000269|PubMed:17990954}.
CC -!- SIMILARITY: Belongs to the isocitrate and isopropylmalate
CC dehydrogenases family. {ECO:0000305}.
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DR EMBL; AB525198; BAI44741.1; -; Genomic_DNA.
DR EMBL; AB525199; BAI44763.1; -; Genomic_DNA.
DR EMBL; AB525200; BAI44805.1; -; Genomic_DNA.
DR AlphaFoldDB; C9K7B7; -.
DR SMR; C9K7B7; -.
DR UniPathway; UPA00048; UER00072.
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-UniPathway.
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 2: Evidence at transcript level;
KW Amino-acid biosynthesis; Branched-chain amino acid biosynthesis;
KW Leucine biosynthesis; Magnesium; Manganese; Metal-binding; NAD; NADP;
KW Oxidoreductase; Virulence.
FT CHAIN 1..373
FT /note="3-isopropylmalate dehydrogenase AMT6"
FT /id="PRO_0000444856"
FT BINDING 77..79
FT /ligand="NADP(+)"
FT /ligand_id="ChEBI:CHEBI:58349"
FT /evidence="ECO:0000250|UniProtKB:O75874"
FT BINDING 97
FT /ligand="substrate"
FT /evidence="ECO:0000250|UniProtKB:O75874"
FT BINDING 136
FT /ligand="substrate"
FT /evidence="ECO:0000250|UniProtKB:P50213"
FT BINDING 227
FT /ligand="Mg(2+)"
FT /ligand_id="ChEBI:CHEBI:18420"
FT /evidence="ECO:0000250|UniProtKB:P50213"
FT BINDING 252
FT /ligand="Mg(2+)"
FT /ligand_id="ChEBI:CHEBI:18420"
FT /evidence="ECO:0000250|UniProtKB:P50213"
FT BINDING 256
FT /ligand="Mg(2+)"
FT /ligand_id="ChEBI:CHEBI:18420"
FT /evidence="ECO:0000250|UniProtKB:P50213"
FT BINDING 284..289
FT /ligand="NADP(+)"
FT /ligand_id="ChEBI:CHEBI:58349"
FT /evidence="ECO:0000250|UniProtKB:O75874"
FT SITE 143
FT /note="Critical for catalysis"
FT /evidence="ECO:0000250|UniProtKB:P50213"
FT SITE 193
FT /note="Critical for catalysis"
FT /evidence="ECO:0000250|UniProtKB:P50213"
SQ SEQUENCE 373 AA; 39267 MW; B031D29B7A6C19AF CRC64;
MKTAHTIVVF GGDYCGPEVM KEGLKVLSEI ERQNPDVKLE LIHHLVGGAA WDVHGENITT
AALSDATSAS AVLLGAVGGP KWAKHAIPVE WGLGRLRKAL DAFGNLRPVN FAAPSLISRS
SLKPKVCTGT EILIVRELTG GVYFGPRSEH DGSFDQASDT DVYTRKEIER VTRLAGSLAM
ARDPPLAVTS LDKANVLAAC GRLWRGVVSE VMAAEFPEIE LRHMLIDSAA MVMALNPTKL
NGVVLASNMF GDIISDQASA IPGSIGLLPS ASLCSIPERG QESSRIRGLY EPIHGSAPDI
AGKGIVNPIG MILSVAMMCR LSLDMGAAAT SIEAAVRDTL EVGICTPDIG GTASTSEVGD
AVVAALVRIF DKH
