ID   NOVS_STRNV              Reviewed;         288 AA.
AC   Q9L9E9;
DT   16-OCT-2013, integrated into UniProtKB/Swiss-Prot.
DT   01-OCT-2000, sequence version 1.
DT   03-AUG-2022, entry version 58.
DE   RecName: Full=dTDP-4-keto-6-deoxy-D-glucose reductase;
DE            EC=1.1.1.-;
DE   AltName: Full=Novobiocin biosynthesis protein S;
GN   Name=novS;
OS   Streptomyces niveus (Streptomyces spheroides).
OC   Bacteria; Actinobacteria; Streptomycetales; Streptomycetaceae;
OC   Streptomyces.
OX   NCBI_TaxID=193462;
RN   [1]
RP   NUCLEOTIDE SEQUENCE [GENOMIC DNA].
RC   STRAIN=ATCC 23965 / DSM 40292 / JCM 4252 / NBRC 12917 / NCIMB 11891 / NRRL
RC   2449;
RX   PubMed=10770754; DOI=10.1128/aac.44.5.1214-1222.2000;
RA   Steffensky M., Muhlenweg A., Wang Z.X., Li S.M., Heide L.;
RT   "Identification of the novobiocin biosynthetic gene cluster of Streptomyces
RT   spheroides NCIB 11891.";
RL   Antimicrob. Agents Chemother. 44:1214-1222(2000).
RN   [2]
RP   FUNCTION, PATHWAY, AND COFACTOR.
RC   STRAIN=ATCC 23965 / DSM 40292 / JCM 4252 / NBRC 12917 / NCIMB 11891 / NRRL
RC   2449;
RX   PubMed=15752721; DOI=10.1016/j.abb.2005.01.012;
RA   Thuy T.T., Lee H.C., Kim C.G., Heide L., Sohng J.K.;
RT   "Functional characterizations of novWUS involved in novobiocin biosynthesis
RT   from Streptomyces spheroides.";
RL   Arch. Biochem. Biophys. 436:161-167(2005).
CC   -!- FUNCTION: Reduces the product formed from the reaction of NovW with
CC       dTDP-4-keto-6-deoxy-D-glucose to result in dTDP-5-methyl-L-rhamnose in
CC       the novobiocin biosynthesis pathway, an aminocoumarin family antibiotic
CC       that targets bacterial DNA gyrases. {ECO:0000269|PubMed:15752721}.
CC   -!- COFACTOR:
CC       Name=Mg(2+); Xref=ChEBI:CHEBI:18420;
CC         Evidence={ECO:0000305|PubMed:15752721};
CC       Note=Binds 1 Mg(2+) ion per monomer. {ECO:0000305|PubMed:15752721};
CC   -!- PATHWAY: Antibiotic biosynthesis; novobiocin biosynthesis.
CC       {ECO:0000269|PubMed:15752721}.
CC   -!- SIMILARITY: Belongs to the dTDP-4-dehydrorhamnose reductase family.
CC       {ECO:0000305}.
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DR   EMBL; AF170880; AAF67512.1; -; Genomic_DNA.
DR   RefSeq; WP_069626147.1; NZ_MDCR01000039.1.
DR   AlphaFoldDB; Q9L9E9; -.
DR   SMR; Q9L9E9; -.
DR   PRIDE; Q9L9E9; -.
DR   KEGG; ag:AAF67512; -.
DR   BioCyc; MetaCyc:MON-18090; -.
DR   UniPathway; UPA01035; -.
DR   GO; GO:0000287; F:magnesium ion binding; IDA:UniProtKB.
DR   GO; GO:0016616; F:oxidoreductase activity, acting on the CH-OH group of donors, NAD or NADP as acceptor; IDA:UniProtKB.
DR   GO; GO:0043642; P:novobiocin biosynthetic process; IDA:UniProtKB.
DR   InterPro; IPR005913; dTDP_dehydrorham_reduct.
DR   InterPro; IPR036291; NAD(P)-bd_dom_sf.
DR   InterPro; IPR029903; RmlD-like-bd.
DR   PANTHER; PTHR10491; PTHR10491; 1.
DR   Pfam; PF04321; RmlD_sub_bind; 1.
DR   SUPFAM; SSF51735; SSF51735; 1.
DR   TIGRFAMs; TIGR01214; rmlD; 1.
PE   3: Inferred from homology;
KW   Antibiotic biosynthesis; Magnesium; Metal-binding; NAD; NADP;
KW   Oxidoreductase.
FT   CHAIN           1..288
FT                   /note="dTDP-4-keto-6-deoxy-D-glucose reductase"
FT                   /id="PRO_0000424009"
FT   ACT_SITE        127
FT                   /note="Proton donor/acceptor"
FT                   /evidence="ECO:0000250|UniProtKB:P26392"
FT   BINDING         12..14
FT                   /ligand="NADH"
FT                   /ligand_id="ChEBI:CHEBI:57945"
FT                   /evidence="ECO:0000250|UniProtKB:P26392"
FT   BINDING         13..14
FT                   /ligand="NADPH"
FT                   /ligand_id="ChEBI:CHEBI:57783"
FT                   /evidence="ECO:0000250|UniProtKB:P26392"
FT   BINDING         38..39
FT                   /ligand="NADH"
FT                   /ligand_id="ChEBI:CHEBI:57945"
FT                   /evidence="ECO:0000250|UniProtKB:P26392"
FT   BINDING         38..39
FT                   /ligand="NADPH"
FT                   /ligand_id="ChEBI:CHEBI:57783"
FT                   /evidence="ECO:0000250|UniProtKB:P26392"
FT   BINDING         62..64
FT                   /ligand="NADH"
FT                   /ligand_id="ChEBI:CHEBI:57945"
FT                   /evidence="ECO:0000250|UniProtKB:P26392"
FT   BINDING         62..64
FT                   /ligand="NADPH"
FT                   /ligand_id="ChEBI:CHEBI:57783"
FT                   /evidence="ECO:0000250|UniProtKB:P26392"
FT   BINDING         127
FT                   /ligand="NADH"
FT                   /ligand_id="ChEBI:CHEBI:57945"
FT                   /evidence="ECO:0000250|UniProtKB:P26392"
FT   BINDING         127
FT                   /ligand="NADPH"
FT                   /ligand_id="ChEBI:CHEBI:57783"
FT                   /evidence="ECO:0000250|UniProtKB:P26392"
FT   BINDING         131
FT                   /ligand="NADH"
FT                   /ligand_id="ChEBI:CHEBI:57945"
FT                   /evidence="ECO:0000250|UniProtKB:P26392"
FT   BINDING         131
FT                   /ligand="NADPH"
FT                   /ligand_id="ChEBI:CHEBI:57783"
FT                   /evidence="ECO:0000250|UniProtKB:P26392"
FT   SITE            103
FT                   /note="Could provide a fine-tuning to achieve optimal pKa
FT                   matching between active site and substrate"
FT                   /evidence="ECO:0000250|UniProtKB:P26392"
SQ   SEQUENCE   288 AA;  31715 MW;  A290297B344C3F4F CRC64;
     MTDRWLVTGA AGMLGRDLVA LLRGLNEPVV AITRHDLDIT DRLSVRAVVD RHRPTTIVNC
     AAWTRFGEAE AGESAALLVN GGGARELAAV CRDRSIRLVH LSTDYVFDGT SRRPYAESAV
     TSPINAYGRT KQAGEQAVLD LLPDDGTIVR TAWLYGRHGM NFIRKMVRLE QLRETVDVVD
     DQWGQPTWTV DLAQQIVALV RHGASGVFHG TSAGEATWYD LARMTFRLLG ADPGRVRPVP
     SDRIAGGELR PRYTVLGHDA WREAGLTPIR HWTTALTQAF PLLNADES