BEA2_BEABA
ID BEA2_BEABA Reviewed; 462 AA.
AC B6D9A7;
DT 25-OCT-2017, integrated into UniProtKB/Swiss-Prot.
DT 25-NOV-2008, sequence version 1.
DT 03-AUG-2022, entry version 47.
DE RecName: Full=Ketoisovalerate reductase {ECO:0000303|PubMed:18804027};
DE Short=KIVR {ECO:0000303|PubMed:18804027};
DE EC=1.2.7.- {ECO:0000269|PubMed:27449895};
GN Name=kivr {ECO:0000303|PubMed:18804027};
OS Beauveria bassiana (White muscardine disease fungus) (Tritirachium
OS shiotae).
OC Eukaryota; Fungi; Dikarya; Ascomycota; Pezizomycotina; Sordariomycetes;
OC Hypocreomycetidae; Hypocreales; Cordycipitaceae; Beauveria.
OX NCBI_TaxID=176275;
RN [1]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA], AND FUNCTION.
RC STRAIN=ATCC 7159;
RX PubMed=18804027; DOI=10.1016/j.chembiol.2008.07.011;
RA Xu Y., Orozco R., Kithsiri Wijeratne E.M., Leslie Gunatilaka A.A.,
RA Stock S.P., Molnar I.;
RT "Biosynthesis of the cyclooligomer depsipeptide beauvericin, a virulence
RT factor of the entomopathogenic fungus Beauveria bassiana.";
RL Chem. Biol. 15:898-907(2008).
RN [2]
RP FUNCTION, AND DISRUPTION PHENOTYPE.
RX PubMed=19105175; DOI=10.1002/cbic.200800570;
RA Xu Y., Wijeratne E.M., Espinosa-Artiles P., Gunatilaka A.A., Molnar I.;
RT "Combinatorial mutasynthesis of scrambled beauvericins, cyclooligomer
RT depsipeptide cell migration inhibitors from Beauveria bassiana.";
RL ChemBioChem 10:345-354(2009).
RN [3]
RP FUNCTION, BIOPHYSICOCHEMICAL PROPERTIES, CATALYTIC ACTIVITY, ACTIVITY
RP REGULATION, SUBUNIT, AND CALMODULIN-BINDING.
RX PubMed=27449895; DOI=10.1111/1462-2920.13461;
RA Kim J., Yoon D.H., Oh J., Hyun M.W., Han J.G., Sung G.H.;
RT "Calmodulin-mediated suppression of 2-ketoisovalerate reductase in
RT Beauveria bassiana beauvericin biosynthetic pathway.";
RL Environ. Microbiol. 18:4136-4143(2016).
RN [4]
RP FUNCTION.
RX PubMed=28534477; DOI=10.1038/ncomms15349;
RA Yu D., Xu F., Zhang S., Zhan J.;
RT "Decoding and reprogramming fungal iterative nonribosomal peptide
RT synthetases.";
RL Nat. Commun. 8:15349-15349(2017).
CC -!- FUNCTION: Ketoisovalerate reductase; part of the gene cluster that
CC mediates the biosynthesis of beauvericin (BEA), a non-ribosomal cyclic
CC hexadepsipeptide that shows antibiotic, antifungal, insecticidal, and
CC cancer cell antiproliferative and antihaptotactic activity
CC (PubMed:18804027, PubMed:19105175, PubMed:27449895). Ketoisovalerate
CC reductase BEA2 catalyzes the NADPH-specific reduction of ketoisovaleric
CC acid to hydroxyisovalerate, a precursor for beauvericin biosynthesis
CC (PubMed:19105175, PubMed:27449895). The nonribosomal cyclodepsipeptide
CC synthetase BEA1 then catalyzes the formation of beauvericin via
CC condensation and cyclization of 3 dipeptidol monomers, each composed of
CC one unit of hydroxyisovalerate and one unit of N-methyl-phenylalanine
CC (PubMed:18804027, PubMed:28534477). {ECO:0000269|PubMed:18804027,
CC ECO:0000269|PubMed:19105175, ECO:0000269|PubMed:27449895,
CC ECO:0000269|PubMed:28534477}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=(R)-2-hydroxy-3-methylbutyrate + NADP(+) = 3-methyl-2-
CC oxobutanoate + H(+) + NADPH; Xref=Rhea:RHEA:62268, ChEBI:CHEBI:11851,
CC ChEBI:CHEBI:15378, ChEBI:CHEBI:57783, ChEBI:CHEBI:58349,
CC ChEBI:CHEBI:145660; Evidence={ECO:0000269|PubMed:27449895};
CC -!- ACTIVITY REGULATION: Environmental stimuli such as light and salt
CC stress suppress activity through stimulation of calmodulin (CaM) that
CC binds BEA2 and probably impairs its dimerization.
CC {ECO:0000269|PubMed:27449895}.
CC -!- BIOPHYSICOCHEMICAL PROPERTIES:
CC pH dependence:
CC Optimum pH is 7.5. {ECO:0000269|PubMed:27449895};
CC Temperature dependence:
CC Optimum temperature is 35 degrees Celsius.
CC {ECO:0000269|PubMed:27449895};
CC -!- SUBUNIT: Homodimer (Probable). Binds to calmodulin in a calcium-
CC independent manner (PubMed:27449895). {ECO:0000269|PubMed:27449895,
CC ECO:0000305|PubMed:27449895}.
CC -!- DISRUPTION PHENOTYPE: Impairs the production of both beauvericin and
CC bassianolide. {ECO:0000269|PubMed:19105175}.
CC -!- SIMILARITY: Belongs to the ketopantoate reductase family.
CC {ECO:0000305}.
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DR EMBL; EU886196; ACI30654.1; -; Genomic_DNA.
DR AlphaFoldDB; B6D9A7; -.
DR STRING; 176275.XP_008603045.1; -.
DR GO; GO:0005516; F:calmodulin binding; IEA:UniProtKB-KW.
DR GO; GO:0016491; F:oxidoreductase activity; IEA:UniProtKB-KW.
DR Gene3D; 1.10.1040.10; -; 1.
DR InterPro; IPR008927; 6-PGluconate_DH-like_C_sf.
DR InterPro; IPR013328; 6PGD_dom2.
DR InterPro; IPR013752; KPA_reductase.
DR InterPro; IPR013332; KPR_N.
DR Pfam; PF02558; ApbA; 1.
DR Pfam; PF08546; ApbA_C; 1.
DR SUPFAM; SSF48179; SSF48179; 1.
PE 1: Evidence at protein level;
KW Calmodulin-binding; NADP; Oxidoreductase.
FT CHAIN 1..462
FT /note="Ketoisovalerate reductase"
FT /id="PRO_0000442152"
FT REGION 34..55
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT MOTIF 167..184
FT /note="Calmoduling-binding"
FT /evidence="ECO:0000269|PubMed:27449895"
FT ACT_SITE 290
FT /note="Proton donor"
FT /evidence="ECO:0000250|UniProtKB:P0A9J4"
FT BINDING 72..77
FT /ligand="NADP(+)"
FT /ligand_id="ChEBI:CHEBI:58349"
FT /evidence="ECO:0000250|UniProtKB:P0A9J4"
FT BINDING 294
FT /ligand="substrate"
FT /evidence="ECO:0000250|UniProtKB:P0A9J4"
FT BINDING 298
FT /ligand="substrate"
FT /evidence="ECO:0000250|UniProtKB:P0A9J4"
FT BINDING 403
FT /ligand="substrate"
FT /evidence="ECO:0000250|UniProtKB:P0A9J4"
FT BINDING 415
FT /ligand="NADP(+)"
FT /ligand_id="ChEBI:CHEBI:58349"
FT /evidence="ECO:0000250|UniProtKB:P0A9J4"
SQ SEQUENCE 462 AA; 51495 MW; 71C60B201516454D CRC64;
MPSPEHPSWL STLLADTRPP PKLFAWSPAN LDSPTAVKPD RADRGDFDPG KYPVDAPITT
ASEPVKRIYI VGPGNVGRLY ASYMSRQRDA LPITLVVHRK ELLSQWVTSE GVVLADRGGK
VTKNKQFDVE WWTESRPRYG PVREVADGEK LHNVFISTKA DAGLGEADRL RRYLGRCSSV
VFAQNGVSKL WAPYGPLYVA SRYHADDAPS FSACVVNHGI SAAGLFYSIH TSPSDAFIGP
IFKGSAAPAH GQNKRRRLDD DFFTTYISST PFLDTKHVSS GQLWIIQLEK LVLNAAINPL
TTLLRCKTGQ LFASYDSHDA LTRVLDQLLW QASAVIQALI NHDANIDMLT SYAETVHRLV
PGSDDYGRNF ANIRRKLTVR FSQPILKAKL YAFGLNIREH RSSMLQDAEA GRKTEIRDVN
GWIVDMAEYL GLDLDVGIHR GLIELIEECV VLDKEELARR LL
