MORA_ASPOR
ID MORA_ASPOR Reviewed; 329 AA.
AC Q2U0N3;
DT 03-AUG-2022, integrated into UniProtKB/Swiss-Prot.
DT 24-JAN-2006, sequence version 1.
DT 03-AUG-2022, entry version 89.
DE RecName: Full=4-methyl-2-oxopentanoate reductase A {ECO:0000303|PubMed:26615399};
DE Short=MOA reductase A {ECO:0000303|PubMed:26615399};
DE Short=MorA {ECO:0000303|PubMed:26615399};
DE EC=1.1.1.272 {ECO:0000269|PubMed:26615399};
DE AltName: Full=2-hydroxyacid dehydrogenase D {ECO:0000303|PubMed:26615399};
DE Short=2-HadhD {ECO:0000303|PubMed:26615399};
GN Name=morA {ECO:0000303|PubMed:26615399}; ORFNames=AO090011000368;
OS Aspergillus oryzae (strain ATCC 42149 / RIB 40) (Yellow koji mold).
OC Eukaryota; Fungi; Dikarya; Ascomycota; Pezizomycotina; Eurotiomycetes;
OC Eurotiomycetidae; Eurotiales; Aspergillaceae; Aspergillus;
OC Aspergillus subgen. Circumdati.
OX NCBI_TaxID=510516;
RN [1]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=ATCC 42149 / RIB 40;
RX PubMed=16372010; DOI=10.1038/nature04300;
RA Machida M., Asai K., Sano M., Tanaka T., Kumagai T., Terai G., Kusumoto K.,
RA Arima T., Akita O., Kashiwagi Y., Abe K., Gomi K., Horiuchi H.,
RA Kitamoto K., Kobayashi T., Takeuchi M., Denning D.W., Galagan J.E.,
RA Nierman W.C., Yu J., Archer D.B., Bennett J.W., Bhatnagar D.,
RA Cleveland T.E., Fedorova N.D., Gotoh O., Horikawa H., Hosoyama A.,
RA Ichinomiya M., Igarashi R., Iwashita K., Juvvadi P.R., Kato M., Kato Y.,
RA Kin T., Kokubun A., Maeda H., Maeyama N., Maruyama J., Nagasaki H.,
RA Nakajima T., Oda K., Okada K., Paulsen I., Sakamoto K., Sawano T.,
RA Takahashi M., Takase K., Terabayashi Y., Wortman J.R., Yamada O.,
RA Yamagata Y., Anazawa H., Hata Y., Koide Y., Komori T., Koyama Y.,
RA Minetoki T., Suharnan S., Tanaka A., Isono K., Kuhara S., Ogasawara N.,
RA Kikuchi H.;
RT "Genome sequencing and analysis of Aspergillus oryzae.";
RL Nature 438:1157-1161(2005).
RN [2]
RP FUNCTION, CATALYTIC ACTIVITY, BIOPHYSICOCHEMICAL PROPERTIES, BIOTECHNOLOGY,
RP AND INDUCTION.
RX PubMed=26615399; DOI=10.1007/s00253-015-7182-0;
RA Shimizu M., Yamamoto T., Okabe N., Sakai K., Koide E., Miyachi Y.,
RA Kurimoto M., Mochizuki M., Yoshino-Yasuda S., Mitsui S., Ito A., Murano H.,
RA Takaya N., Kato M.;
RT "Novel 4-methyl-2-oxopentanoate reductase involved in synthesis of the
RT Japanese sake flavor, ethyl leucate.";
RL Appl. Microbiol. Biotechnol. 100:3137-3145(2016).
CC -!- FUNCTION: 4-methyl-2-oxopentanoate (MOA) reductase that reduces MOA, a
CC possible intermediate in leucine synthesis, to D-leucate in a NADPH- or
CC NADH-dependent manner, but with a preference for NADPH
CC (PubMed:26615399). In addition to MOA, shows broad substrate
CC specificity toward 2-keto acids (PubMed:26615399).
CC {ECO:0000269|PubMed:26615399}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=(R)-2-hydroxy-4-methylpentanoate + NADP(+) = 4-methyl-2-
CC oxopentanoate + H(+) + NADPH; Xref=Rhea:RHEA:12873,
CC ChEBI:CHEBI:15378, ChEBI:CHEBI:17865, ChEBI:CHEBI:55535,
CC ChEBI:CHEBI:57783, ChEBI:CHEBI:58349; EC=1.1.1.272;
CC Evidence={ECO:0000269|PubMed:26615399};
CC PhysiologicalDirection=right-to-left; Xref=Rhea:RHEA:12875;
CC Evidence={ECO:0000269|PubMed:26615399};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=a (2R)-2-hydroxycarboxylate + NADP(+) = a 2-oxocarboxylate +
CC H(+) + NADPH; Xref=Rhea:RHEA:35735, ChEBI:CHEBI:15378,
CC ChEBI:CHEBI:35179, ChEBI:CHEBI:57783, ChEBI:CHEBI:58314,
CC ChEBI:CHEBI:58349; EC=1.1.1.272;
CC Evidence={ECO:0000269|PubMed:26615399};
CC PhysiologicalDirection=right-to-left; Xref=Rhea:RHEA:35737;
CC Evidence={ECO:0000269|PubMed:26615399};
CC -!- BIOPHYSICOCHEMICAL PROPERTIES:
CC Kinetic parameters:
CC KM=4.1 mM for 4-methyl-2-oxopentanoate (MOA)
CC {ECO:0000269|PubMed:26615399};
CC KM=61.0 mM for pyruvate {ECO:0000269|PubMed:26615399};
CC KM=0.53 mM for hydroxypyruvate {ECO:0000269|PubMed:26615399};
CC KM=0.75 mM for glyoxylate {ECO:0000269|PubMed:26615399};
CC KM=20.0 mM for 3-methyl-2-oxovalerate {ECO:0000269|PubMed:26615399};
CC KM=1.61 mM for phenylpyruvate {ECO:0000269|PubMed:26615399};
CC KM=0.012 mM for NADPH {ECO:0000269|PubMed:26615399};
CC KM=0.15 mM for NADH {ECO:0000269|PubMed:26615399};
CC Note=kcat is 15.0 sec(-1) with 4-methyl-2-oxopentanoate (MOA) as
CC substrate. kcat is 140.0 sec(-1) with pyruvate as substrate. kcat is
CC 10.0 sec(-1) with hydroxypyruvate as substrate. kcat is 11.0 sec(-1)
CC with glyoxylate as substrate. kcat is 0.74 sec(-1) with 3-methyl-2-
CC oxovalerate as substrate. kcat is 12.0 sec(-1) with phenylpyruvate as
CC substrate. kcat is 140.0 sec(-1) with NADPH as substrate. kcat is
CC 22.0 sec(-1) with NADH as substrate. {ECO:0000269|PubMed:26615399};
CC pH dependence:
CC Optimum pH is 4.5 to 6.0. {ECO:0000269|PubMed:26615399};
CC -!- INDUCTION: Leucine and 4-methyl-2-oxopentanate (MOA) increase the
CC expression 3.1- and 4.5-fold, respectively, whereas leucate represses
CC the expression. {ECO:0000269|PubMed:26615399}.
CC -!- BIOTECHNOLOGY: Ethyl-2-hydroxy-4-methylpentanoate (ethyl leucate)
CC contributes to a fruity flavor in Japanese sake and the strain
CC overexpressing morA would help to ferment high-quality sake with an
CC excellent flavor. {ECO:0000269|PubMed:26615399}.
CC -!- SIMILARITY: Belongs to the D-isomer specific 2-hydroxyacid
CC dehydrogenase family. {ECO:0000305}.
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DR EMBL; AP007171; BAE64882.1; -; Genomic_DNA.
DR RefSeq; XP_001826015.1; XM_001825963.2.
DR SMR; Q2U0N3; -.
DR STRING; 510516.Q2U0N3; -.
DR EnsemblFungi; BAE64882; BAE64882; AO090011000368.
DR GeneID; 5998118; -.
DR KEGG; aor:AO090011000368; -.
DR VEuPathDB; FungiDB:AO090011000368; -.
DR HOGENOM; CLU_019796_1_2_1; -.
DR OMA; PHIAWAY; -.
DR BioCyc; MetaCyc:MON-19754; -.
DR Proteomes; UP000006564; Chromosome 7.
DR GO; GO:0051287; F:NAD binding; IEA:InterPro.
DR GO; GO:0016616; F:oxidoreductase activity, acting on the CH-OH group of donors, NAD or NADP as acceptor; IEA:InterPro.
DR InterPro; IPR006139; D-isomer_2_OHA_DH_cat_dom.
DR InterPro; IPR029753; D-isomer_DH_CS.
DR InterPro; IPR029752; D-isomer_DH_CS1.
DR InterPro; IPR006140; D-isomer_DH_NAD-bd.
DR InterPro; IPR036291; NAD(P)-bd_dom_sf.
DR Pfam; PF00389; 2-Hacid_dh; 1.
DR Pfam; PF02826; 2-Hacid_dh_C; 1.
DR SUPFAM; SSF51735; SSF51735; 1.
DR PROSITE; PS00065; D_2_HYDROXYACID_DH_1; 1.
DR PROSITE; PS00671; D_2_HYDROXYACID_DH_3; 1.
PE 1: Evidence at protein level;
KW NAD; Oxidoreductase; Reference proteome.
FT CHAIN 1..329
FT /note="4-methyl-2-oxopentanoate reductase A"
FT /id="PRO_0000455827"
FT ACT_SITE 242
FT /evidence="ECO:0000250|UniProtKB:Q9I3W9"
FT ACT_SITE 271
FT /evidence="ECO:0000250|UniProtKB:Q9I3W9"
FT ACT_SITE 289
FT /note="Proton donor"
FT /evidence="ECO:0000250|UniProtKB:Q9I3W9"
FT BINDING 162..163
FT /ligand="NAD(+)"
FT /ligand_id="ChEBI:CHEBI:57540"
FT /evidence="ECO:0000250|UniProtKB:Q9I3W9"
FT BINDING 240..242
FT /ligand="NAD(+)"
FT /ligand_id="ChEBI:CHEBI:57540"
FT /evidence="ECO:0000250|UniProtKB:Q9I3W9"
FT BINDING 266
FT /ligand="NAD(+)"
FT /ligand_id="ChEBI:CHEBI:57540"
FT /evidence="ECO:0000250|UniProtKB:Q9I3W9"
SQ SEQUENCE 329 AA; 35853 MW; 4FF1A7306D26C35B CRC64;
MPSALLIGEI THARKEWEEL SSILTLTEFP SGTREDFIRN CKEGQYDDVL VIYRSNTSTK
FTGPFDAELL AVLPKSLKYI CHNGAGYDNI DVKGCTDKGI AVSSTPVAVN HATADVGIFL
MIGALRQAYV PLSALRAGQW QGQTTLGRDP QGKVLGILGM GGIGREMANR AKAFGMKIQY
HNRSRLSPEL EGDATYVSFD ELLASSDVLS LNLALNASTR HIIGEKEFQK MKDGIVIVNT
ARGALIDEKA LVAALDSGKV LSAGLDVYEN EPVVEQGLVN NPKVMLLPHI GTMTYETQKD
MELLVLNNLR SAVEKGKMIT LVPEQKNVF
