VLMH_STRVF
ID VLMH_STRVF Reviewed; 378 AA.
AC P96072;
DT 28-MAR-2018, integrated into UniProtKB/Swiss-Prot.
DT 01-MAY-1997, sequence version 1.
DT 03-AUG-2022, entry version 79.
DE RecName: Full=Isobutylamine N-hydroxylase {ECO:0000303|PubMed:9056232};
DE Short=IBAH {ECO:0000303|PubMed:8990292};
DE EC=1.14.14.30 {ECO:0000269|PubMed:8990292, ECO:0000269|PubMed:9056232};
DE AltName: Full=Flavin monooxygenase {ECO:0000303|PubMed:9056232};
DE AltName: Full=Isobutylamine N-hydroxylase, monooxygenase component {ECO:0000305|PubMed:9056232};
GN Name=vlmH {ECO:0000303|PubMed:8990292};
OS Streptomyces viridifaciens.
OC Bacteria; Actinobacteria; Streptomycetales; Streptomycetaceae;
OC Streptomyces.
OX NCBI_TaxID=48665 {ECO:0000312|EMBL:AAN10237.1};
RN [1]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA], PROTEIN SEQUENCE OF 1-45, FUNCTION,
RP CATALYTIC ACTIVITY, ACTIVITY REGULATION, SUBSTRATE SPECIFICITY, AND
RP SUBUNIT.
RC STRAIN=MG456-hF10 {ECO:0000312|EMBL:AAN10237.1};
RX PubMed=9056232; DOI=10.1006/abbi.1996.9857;
RA Parry R.J., Li W.;
RT "Purification and characterization of isobutylamine N-hydroxylase from the
RT valanimycin producer Streptomyces viridifaciens MG456-hF10.";
RL Arch. Biochem. Biophys. 339:47-54(1997).
RN [2]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA], PROTEIN SEQUENCE OF 1-45, FUNCTION, AND
RP CATALYTIC ACTIVITY.
RC STRAIN=MG456-hF10 {ECO:0000312|EMBL:AAN10237.1};
RX PubMed=8990292; DOI=10.1128/jb.179.2.409-416.1997;
RA Parry R.J., Li W., Cooper H.N.;
RT "Cloning, analysis, and overexpression of the gene encoding isobutylamine
RT N-hydroxylase from the valanimycin producer, Streptomyces viridifaciens.";
RL J. Bacteriol. 179:409-416(1997).
RN [3]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA].
RC STRAIN=MG456-hF10 {ECO:0000312|EMBL:AAN10237.1};
RX PubMed=10708373; DOI=10.1099/00221287-146-2-345;
RA Ma Y., Patel J., Parry R.J.;
RT "A novel valanimycin-resistance determinant (vlmF) from Streptomyces
RT viridifaciens MG456-hF10.";
RL Microbiology 146:345-352(2000).
RN [4]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA].
RC STRAIN=MG456-hF10 {ECO:0000312|EMBL:AAN10237.1};
RX PubMed=12406225; DOI=10.1046/j.1365-2958.2002.03169.x;
RA Garg R.P., Ma Y., Hoyt J.C., Parry R.J.;
RT "Molecular characterization and analysis of the biosynthetic gene cluster
RT for the azoxy antibiotic valanimycin.";
RL Mol. Microbiol. 46:505-517(2002).
RN [5]
RP FUNCTION.
RX PubMed=9287340; DOI=10.1074/jbc.272.37.23303;
RA Parry R.J., Li W.;
RT "An NADPH:FAD oxidoreductase from the valanimycin producer, Streptomyces
RT viridifaciens. Cloning, analysis, and overexpression.";
RL J. Biol. Chem. 272:23303-23311(1997).
CC -!- FUNCTION: Involved in the biosynthesis of the azoxy antibiotic
CC valanimycin, which has an antitumor activity (PubMed:9056232,
CC PubMed:8990292, PubMed:9287340). Catalyzes the oxidation of
CC isobutylamine to isobutylhydroxylamine via the formation of a flavin
CC 4a-hydroperoxide (PubMed:9056232, PubMed:8990292, PubMed:9287340).
CC Unlike other known N-hydroxylases, isobutylamine N-hydroxylase cannot
CC carry out the reduction of the flavin cofactor and requires the NADPH-
CC flavin oxidoreductase VlmR (PubMed:9056232). Also able to oxidize
CC propan-1-amine, butan-1-amine, butan-2-amine and benzylamine
CC (PubMed:9056232). It has a similar activity with either FMNH(2) or
CC FADH(2) (PubMed:9056232). {ECO:0000269|PubMed:8990292,
CC ECO:0000269|PubMed:9056232, ECO:0000269|PubMed:9287340}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=2-methylpropan-1-amine + FADH2 + O2 = FAD + 2 H(+) + H2O + N-
CC (2-methylpropyl)hydroxylamine; Xref=Rhea:RHEA:48864,
CC ChEBI:CHEBI:15377, ChEBI:CHEBI:15378, ChEBI:CHEBI:15379,
CC ChEBI:CHEBI:57601, ChEBI:CHEBI:57692, ChEBI:CHEBI:58307,
CC ChEBI:CHEBI:131928; EC=1.14.14.30;
CC Evidence={ECO:0000269|PubMed:8990292, ECO:0000269|PubMed:9056232};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=2-methylpropan-1-amine + FMNH2 + O2 = FMN + 2 H(+) + H2O + N-
CC (2-methylpropyl)hydroxylamine; Xref=Rhea:RHEA:49804,
CC ChEBI:CHEBI:15377, ChEBI:CHEBI:15378, ChEBI:CHEBI:15379,
CC ChEBI:CHEBI:57601, ChEBI:CHEBI:57618, ChEBI:CHEBI:58210,
CC ChEBI:CHEBI:131928; EC=1.14.14.30;
CC Evidence={ECO:0000269|PubMed:8990292, ECO:0000269|PubMed:9056232};
CC -!- ACTIVITY REGULATION: Inhibited by 5',5'-dithio-bis(2-nitrobenzoic acid)
CC (DTNB) and 4-(hydroxymercuri)benzoic acid (p-HMB).
CC {ECO:0000269|PubMed:9056232}.
CC -!- SUBUNIT: Exists in dimeric or trimeric form depending upon buffer
CC conditions (PubMed:9056232). It can form an isobutylamine N-hydroxylase
CC two component enzyme system formed of a flavin reductase component
CC (VlmR) and a monooxygenase component (VlmH).
CC {ECO:0000269|PubMed:9056232}.
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DR EMBL; AY116644; AAN10237.1; -; Genomic_DNA.
DR AlphaFoldDB; P96072; -.
DR SMR; P96072; -.
DR KEGG; ag:AAN10237; -.
DR BioCyc; MetaCyc:MON-17644; -.
DR GO; GO:0050660; F:flavin adenine dinucleotide binding; IEA:InterPro.
DR GO; GO:0016627; F:oxidoreductase activity, acting on the CH-CH group of donors; IEA:InterPro.
DR GO; GO:0017000; P:antibiotic biosynthetic process; IEA:UniProtKB-KW.
DR Gene3D; 1.10.540.10; -; 1.
DR Gene3D; 2.40.110.10; -; 1.
DR InterPro; IPR046373; Acyl-CoA_Oxase/DH_mid-dom_sf.
DR InterPro; IPR036250; AcylCo_DH-like_C.
DR InterPro; IPR013786; AcylCoA_DH/ox_N.
DR InterPro; IPR037069; AcylCoA_DH/ox_N_sf.
DR InterPro; IPR009100; AcylCoA_DH/oxidase_NM_dom.
DR Pfam; PF02771; Acyl-CoA_dh_N; 1.
DR SUPFAM; SSF47203; SSF47203; 1.
DR SUPFAM; SSF56645; SSF56645; 1.
PE 1: Evidence at protein level;
KW Antibiotic biosynthesis; Direct protein sequencing; FAD; Flavoprotein; FMN;
KW Oxidoreductase.
FT CHAIN 1..378
FT /note="Isobutylamine N-hydroxylase"
FT /id="PRO_0000443526"
SQ SEQUENCE 378 AA; 39890 MW; 070F546A7A155A66 CRC64;
MRSLDAARDT CERLHPGLIK ALEELPLLER EAEGSPVLDI FRAHGGAGLL VPSAYGGHGA
DALDAVRVTR ALGACSPSLA AAATMHNFTA AMLFALTDRV IPPTDEQKKL LARVAPEGML
LASGWAEGRT QQDILNPSVK ATPVDDGFIL NGSKKPCSLS RSMDILTASV ILPDETGQQS
LAVPLIMADS PGISVHPFWE SPVLAGSQSN EVRLKDVHVP EKLIIRGTPD DPGRLDDLQT
ATFVWFELLI TSAYVGAASA LTELVMERDR GSVTDRAALG IQLESAVGLT EGVARAVRDG
VFGEEAVAAA LTARFAVQKT LAAISDQAIE LLGGIAFIKS PELAYLSSAL HPLAFHPPGR
TSSSPHLVEY FSGGPLEI
