ID   NOVJ_STRNV              Reviewed;         262 AA.
AC   Q9L9F8;
DT   16-OCT-2013, integrated into UniProtKB/Swiss-Prot.
DT   01-OCT-2000, sequence version 1.
DT   03-AUG-2022, entry version 77.
DE   RecName: Full=Short-chain reductase protein NovJ;
DE            EC=1.1.1.-;
DE   AltName: Full=Novobiocin biosynthesis protein J;
GN   Name=novJ;
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, CATALYTIC ACTIVITY, ACTIVE SITE, PATHWAY, SUBUNIT, AND
RP   MUTAGENESIS OF SER-152; TYR-164 AND LYS-168.
RC   STRAIN=ATCC 23965 / DSM 40292 / JCM 4252 / NBRC 12917 / NCIMB 11891 / NRRL
RC   2449;
RX   PubMed=16171397; DOI=10.1021/bi051297m;
RA   Pacholec M., Hillson N.J., Walsh C.T.;
RT   "NovJ/NovK catalyze benzylic oxidation of a beta-hydroxyl tyrosyl-S-
RT   pantetheinyl enzyme during aminocoumarin ring formation in novobiocin
RT   biosynthesis.";
RL   Biochemistry 44:12819-12826(2005).
CC   -!- FUNCTION: Catalytic subunit of the NovJ(2)K(2) heterotetramer that
CC       catalyzes the NADPH-dependent reduction of the tyrosyl moiety of L-
CC       beta-OH-Tyr-S-NovH intermediate to yield the tethered beta-ketotyrosyl-
CC       S-NovH in the novobiocin biosynthesis pathway. Novobiocin is an
CC       aminocoumarin family antibiotic that targets bacterial DNA gyrases.
CC       {ECO:0000269|PubMed:16171397}.
CC   -!- PATHWAY: Antibiotic biosynthesis; novobiocin biosynthesis.
CC       {ECO:0000269|PubMed:16171397}.
CC   -!- SUBUNIT: Heterotetramer; the NovJ(2)K(2) heterotetramer is composed of
CC       subunits of 2 NovJ and 2 subunits of NovK.
CC       {ECO:0000269|PubMed:16171397}.
CC   -!- SIMILARITY: Belongs to the short-chain dehydrogenases/reductases (SDR)
CC       family. {ECO:0000305}.
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DR   EMBL; AF170880; AAF67503.1; -; Genomic_DNA.
DR   RefSeq; WP_069626140.1; NZ_MDCR01000039.1.
DR   AlphaFoldDB; Q9L9F8; -.
DR   SMR; Q9L9F8; -.
DR   KEGG; ag:AAF67503; -.
DR   BioCyc; MetaCyc:MON-18082; -.
DR   UniPathway; UPA01035; -.
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; IPR036291; NAD(P)-bd_dom_sf.
DR   InterPro; IPR020904; Sc_DH/Rdtase_CS.
DR   InterPro; IPR002347; SDR_fam.
DR   PRINTS; PR00081; GDHRDH.
DR   PRINTS; PR00080; SDRFAMILY.
DR   SUPFAM; SSF51735; SSF51735; 1.
DR   PROSITE; PS00061; ADH_SHORT; 1.
PE   1: Evidence at protein level;
KW   Antibiotic biosynthesis; NADP; Oxidoreductase.
FT   CHAIN           1..262
FT                   /note="Short-chain reductase protein NovJ"
FT                   /id="PRO_0000423995"
FT   ACT_SITE        164
FT                   /note="Proton acceptor"
FT                   /evidence="ECO:0000305|PubMed:16171397"
FT   BINDING         23..26
FT                   /ligand="NADP(+)"
FT                   /ligand_id="ChEBI:CHEBI:58349"
FT                   /evidence="ECO:0000250"
FT   BINDING         73..74
FT                   /ligand="NADP(+)"
FT                   /ligand_id="ChEBI:CHEBI:58349"
FT                   /evidence="ECO:0000250"
FT   BINDING         152
FT                   /ligand="substrate"
FT                   /evidence="ECO:0000305"
FT   BINDING         164..168
FT                   /ligand="NADP(+)"
FT                   /ligand_id="ChEBI:CHEBI:58349"
FT                   /evidence="ECO:0000250"
FT   MUTAGEN         152
FT                   /note="S->A: 2-3-fold decrease in beta-ketotyrosine product
FT                   formation."
FT                   /evidence="ECO:0000269|PubMed:16171397"
FT   MUTAGEN         164
FT                   /note="Y->F: 50-fold reduction in catalytic activity."
FT                   /evidence="ECO:0000269|PubMed:16171397"
FT   MUTAGEN         168
FT                   /note="K->I: Does not alter the catalytic turnover."
FT                   /evidence="ECO:0000269|PubMed:16171397"
SQ   SEQUENCE   262 AA;  26850 MW;  FB86B3336F66FDBD CRC64;
     MTSPADATTE VAVSQESVAM VTGAGRGIGA ATAERLAAEG MAVIVVDRTE QDTRATVAAI
     RTAGGRARGI GCDVAVAQAV TAAVATAVEE FGRIDVLVNC AGINRDRLLL TMGDQEWDTV
     LDVNLGGTMR CSFAVGRHMR RQGHGRIINF SSVAARGNAG QTNYATAKGA IAGFTRTLAA
     ELGPHGVTVN AIAPGFVATP MVDELAERLG GDRDSVMSEA AKSSAVGRIG TPEEIAATVV
     FVARPESGYL TGETVHVDGG RP