ID NOVH_STRNV Reviewed; 600 AA.
AC Q9L9G0;
DT 16-OCT-2013, integrated into UniProtKB/Swiss-Prot.
DT 11-JUL-2012, sequence version 2.
DT 13-SEP-2023, entry version 96.
DE RecName: Full=Novobiocin biosynthesis protein H;
DE EC=6.-.-.-;
GN Name=novH;
OS Streptomyces niveus (Streptomyces spheroides).
OC Bacteria; Actinomycetota; Actinomycetes; Kitasatosporales;
OC Streptomycetaceae; 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 BIOPHYSICOCHEMICAL PROPERTIES.
RC STRAIN=ATCC 23965 / DSM 40292 / JCM 4252 / NBRC 12917 / NCIMB 11891 / NRRL
RC 2449;
RX PubMed=11325587; DOI=10.1016/s1074-5521(01)00009-6;
RA Chen H., Walsh C.T.;
RT "Coumarin formation in novobiocin biosynthesis: beta-hydroxylation of the
RT aminoacyl enzyme tyrosyl-S-NovH by a cytochrome P450 NovI.";
RL Chem. Biol. 8:301-312(2001).
CC -!- FUNCTION: Together with NovI, involved in the formation of a beta-OH-
CC Tyr intermediate in the novobiocin biosynthesis pathway, an
CC aminocoumarin family antibiotic that targets bacterial DNA gyrases. The
CC ATP-dependent AMP-binding region activates L-Tyr as L-tyrosyl-AMP and
CC then transfers the L-tyrosyl group to the acyl carrier domain through
CC thioester formation to form a tyrosyl-S intermediate that is covalently
CC tethered to NovH (L-Tyr-S-NovH). {ECO:0000269|PubMed:11325587}.
CC -!- BIOPHYSICOCHEMICAL PROPERTIES:
CC Kinetic parameters:
CC KM=1.39 mM for L-Tyr {ECO:0000269|PubMed:11325587};
CC KM=0.84 mM for p-Br-DL-Phe {ECO:0000269|PubMed:11325587};
CC KM=0.89 mM for L-Phe {ECO:0000269|PubMed:11325587};
CC KM=2.17 mM for 3-Cl-L-Tyr {ECO:0000269|PubMed:11325587};
CC KM=6.13 mM for 3-Me-L-Tyr {ECO:0000269|PubMed:11325587};
CC Note=kcat is 15 min(-1) with L-Tyr as substrate. kcat is 0.44 min(-1)
CC with p-Br-DL-Phe as substrate. kcat is 0.13 min(-1) with L-Phe as
CC substrate. kcat is 0.23 min(-1) with 3-Cl-L-Tyr as substrate. kcat is
CC 0.0083 min(-1) with 3-Me-L-Tyr as substrate.;
CC -!- PATHWAY: Antibiotic biosynthesis; novobiocin biosynthesis.
CC {ECO:0000269|PubMed:11325587}.
CC -!- SIMILARITY: Belongs to the ATP-dependent AMP-binding enzyme family.
CC {ECO:0000305}.
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DR EMBL; AF170880; AAF67501.2; -; Genomic_DNA.
DR AlphaFoldDB; Q9L9G0; -.
DR SMR; Q9L9G0; -.
DR KEGG; ag:AAF67501; -.
DR BioCyc; MetaCyc:MONOMER-18084; -.
DR UniPathway; UPA01035; -.
DR GO; GO:0016874; F:ligase activity; IDA:UniProtKB.
DR GO; GO:0043642; P:novobiocin biosynthetic process; IDA:UniProtKB.
DR CDD; cd17652; A_NRPS_CmdD_like; 1.
DR Gene3D; 3.30.300.30; -; 1.
DR Gene3D; 1.10.1200.10; ACP-like; 1.
DR Gene3D; 3.40.50.12780; N-terminal domain of ligase-like; 1.
DR InterPro; IPR010071; AA_adenyl_domain.
DR InterPro; IPR036736; ACP-like_sf.
DR InterPro; IPR025110; AMP-bd_C.
DR InterPro; IPR045851; AMP-bd_C_sf.
DR InterPro; IPR020459; AMP-binding.
DR InterPro; IPR020845; AMP-binding_CS.
DR InterPro; IPR000873; AMP-dep_Synth/Lig_com.
DR InterPro; IPR042099; ANL_N_sf.
DR InterPro; IPR009081; PP-bd_ACP.
DR InterPro; IPR006162; Ppantetheine_attach_site.
DR NCBIfam; TIGR01733; AA-adenyl-dom; 1.
DR PANTHER; PTHR45527:SF1; FATTY ACID SYNTHASE; 1.
DR PANTHER; PTHR45527; NONRIBOSOMAL PEPTIDE SYNTHETASE; 1.
DR Pfam; PF00501; AMP-binding; 1.
DR Pfam; PF13193; AMP-binding_C; 1.
DR Pfam; PF00550; PP-binding; 1.
DR PRINTS; PR00154; AMPBINDING.
DR SUPFAM; SSF56801; Acetyl-CoA synthetase-like; 1.
DR SUPFAM; SSF47336; ACP-like; 1.
DR PROSITE; PS00455; AMP_BINDING; 1.
DR PROSITE; PS50075; CARRIER; 1.
DR PROSITE; PS00012; PHOSPHOPANTETHEINE; 1.
PE 1: Evidence at protein level;
KW Antibiotic biosynthesis; Ligase; Phosphopantetheine; Phosphoprotein.
FT CHAIN 1..600
FT /note="Novobiocin biosynthesis protein H"
FT /id="PRO_0000423997"
FT DOMAIN 526..600
FT /note="Carrier"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00258"
FT REGION 505..526
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT MOD_RES 561
FT /note="O-(pantetheine 4'-phosphoryl)serine"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00258"
SQ SEQUENCE 600 AA; 63315 MW; 195E16673ECBF319 CRC64;
MFNTRANKAS DQSPTIPTES ATLAELWERT VRSRPSSPAI VTNGETLSYD EVNARANRLA
RLLLDEGAGP GRLVALALPR SSHLVISVLA VAKAGAVFLP LDVNHPRERL SYQLADARPA
LLCTVRSAAA RLPDGIEMPR VLLDSPERTA VLDALPDTDL TDDERGGPLA ATDLAYVIYT
SGSTGRPKGV ALTGAGLPAL AAAKVAAMRV TGDSRVLQFA SPGFDAYLTE LLAAFTAGAT
LVVPGTDTLA GDPLRRALRD GRVSHAVLPP AAVATMSPDA VPDLRVLVVA GEACPAGLVE
RWAPGRLLIN AYGPTECTVC ATMTGPLTPT DEVTIGRPIP GVSVYILDAE RRPAAPGEIG
ELYLSGAGLA QGYLNSPDLT AQMFVPNPFA ADGERMYRTG DLASRRADGD ILFHGRIDDQ
VELRGFRVEL GEVESVLSQH PDVAQAVAAL WTDPAEGPQL VTYVVPAPGT TPSAGELREH
AGRFLPDFMV PSAFTTIDAV PLTPGGKTDR AGLPDPVKAT QPAGLGPRTP AEKVLCDIFR
DLFDLVEIDV RSNFFEMGGN SILAVDLIQR AQEAGLTLMP RTVIDHPTIE QLAAIATLEE
//
