NCSB2_STRCZ
ID NCSB2_STRCZ Reviewed; 558 AA.
AC Q84HC5;
DT 29-OCT-2014, integrated into UniProtKB/Swiss-Prot.
DT 01-JUN-2003, sequence version 1.
DT 03-AUG-2022, entry version 48.
DE RecName: Full=2-hydroxy-7-methoxy-5-methyl-1-naphthoate--CoA ligase {ECO:0000305};
DE EC=6.2.1.43 {ECO:0000269|PubMed:17539640};
DE AltName: Full=Neocarzinostatin biosynthesis protein B2 {ECO:0000305};
GN Name=ncsB2 {ECO:0000303|PubMed:15797213};
OS Streptomyces carzinostaticus.
OC Bacteria; Actinobacteria; Streptomycetales; Streptomycetaceae;
OC Streptomyces.
OX NCBI_TaxID=1897;
RN [1]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA], AND PATHWAY.
RC STRAIN=ATCC 15944 / E-793 / F-51;
RX PubMed=15797213; DOI=10.1016/j.chembiol.2004.12.013;
RA Liu W., Nonaka K., Nie L., Zhang J., Christenson S.D., Bae J.,
RA Van Lanen S.G., Zazopoulos E., Farnet C.M., Yang C.F., Shen B.;
RT "The neocarzinostatin biosynthetic gene cluster from Streptomyces
RT carzinostaticus ATCC 15944 involving two iterative type I polyketide
RT synthases.";
RL Chem. Biol. 12:293-302(2005).
RN [2]
RP FUNCTION, CATALYTIC ACTIVITY, AND BIOPHYSICOCHEMICAL PROPERTIES.
RX PubMed=17539640; DOI=10.1021/ja071886a;
RA Cooke H.A., Zhang J., Griffin M.A., Nonaka K., Van Lanen S.G., Shen B.,
RA Bruner S.D.;
RT "Characterization of NcsB2 as a promiscuous naphthoic acid/coenzyme A
RT ligase integral to the biosynthesis of the enediyne antitumor antibiotic
RT neocarzinostatin.";
RL J. Am. Chem. Soc. 129:7728-7729(2007).
CC -!- FUNCTION: Catalyzes the activation of 2-hydroxy-7-methoxy-5-methyl-1-
CC naphthoate in the biosynthesis of the naphthoate moiety of the
CC neocarzinostatin chromophore. Also catalyzes the activation of other 1-
CC naphthoic acid analogs such as 2-hydroxy-5-methyl-1-naphthoate or 2,7-
CC dihydroxy-5-methyl-1-naphthoate in vitro.
CC {ECO:0000269|PubMed:17539640}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=2-hydroxy-7-methoxy-5-methyl-1-naphthoate + ATP + CoA = 2-
CC hydroxy-7-methoxy-5-methyl-1-naphthoyl-CoA + AMP + diphosphate;
CC Xref=Rhea:RHEA:41644, ChEBI:CHEBI:30616, ChEBI:CHEBI:33019,
CC ChEBI:CHEBI:57287, ChEBI:CHEBI:78282, ChEBI:CHEBI:78376,
CC ChEBI:CHEBI:456215; EC=6.2.1.43;
CC Evidence={ECO:0000269|PubMed:17539640};
CC -!- BIOPHYSICOCHEMICAL PROPERTIES:
CC Kinetic parameters:
CC KM=0.59 uM for 2-hydroxy-7-methoxy-5-methyl-1-naphthoate
CC {ECO:0000269|PubMed:17539640};
CC KM=0.25 uM for 2-hydroxy-5-methyl-1-naphthoate
CC {ECO:0000269|PubMed:17539640};
CC KM=3.1 uM for 2,7-dihydroxy-5-methyl-1-naphthoate
CC {ECO:0000269|PubMed:17539640};
CC Note=kcat is 38 min(-1) with 2-hydroxy-7-methoxy-5-methyl-1-
CC naphthoate as substrate. kcat is 8.1 min(-1) with 2-hydroxy-5-methyl-
CC 1-naphthoate as substrate. kcat is 93 min(-1) with 2,7-dihydroxy-5-
CC methyl-1-naphthoate as substrate. {ECO:0000269|PubMed:17539640};
CC -!- PATHWAY: Antibiotic biosynthesis. {ECO:0000305|PubMed:15797213}.
CC -!- SIMILARITY: Belongs to the ATP-dependent AMP-binding enzyme family.
CC {ECO:0000305}.
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DR EMBL; AY117439; AAM77987.1; -; Genomic_DNA.
DR AlphaFoldDB; Q84HC5; -.
DR SMR; Q84HC5; -.
DR KEGG; ag:AAM77987; -.
DR GO; GO:0016878; F:acid-thiol ligase activity; IDA:UniProtKB.
DR GO; GO:0005524; F:ATP binding; IEA:UniProtKB-KW.
DR GO; GO:0017000; P:antibiotic biosynthetic process; IDA:UniProtKB.
DR Gene3D; 3.30.300.30; -; 1.
DR InterPro; IPR025110; AMP-bd_C.
DR InterPro; IPR045851; AMP-bd_C_sf.
DR InterPro; IPR020845; AMP-binding_CS.
DR InterPro; IPR000873; AMP-dep_Synth/Lig.
DR Pfam; PF00501; AMP-binding; 1.
DR Pfam; PF13193; AMP-binding_C; 1.
DR PROSITE; PS00455; AMP_BINDING; 1.
PE 1: Evidence at protein level;
KW Antibiotic biosynthesis; ATP-binding; Ligase; Nucleotide-binding.
FT CHAIN 1..558
FT /note="2-hydroxy-7-methoxy-5-methyl-1-naphthoate--CoA
FT ligase"
FT /id="PRO_0000430702"
FT BINDING 212..213
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000250|UniProtKB:P40871"
FT BINDING 329..331
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000250|UniProtKB:P40871"
FT BINDING 351
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000250|UniProtKB:P40871"
FT BINDING 435
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000250|UniProtKB:P40871"
FT BINDING 450
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000250|UniProtKB:P40871"
FT BINDING 542
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000250|UniProtKB:P40871"
SQ SEQUENCE 558 AA; 59990 MW; 02629ED7340F05F5 CRC64;
MHETAAAPAP AGFVPWPDDV AARYTAAGHW EGRSLGTHLA EAARKVPEAV CLVDGPVRMS
YSELMARADG AAVRMRGLGI RPADRVVVQL PNCWEHVVVT MACLRLGALP IWALPQYRHR
ELSGVVTHAR ASALVVPDVY REFDHQALAH EVAEAQPTVR HVLVAGSDVR PDSVDLRALC
EPLDADEAAR VAAELDRSAP RGEEVAMLKL SGGTTGLPKL VARTHNDLSY MIKRAAQVCG
FGRDTVYLAV LPLGHGFPNT GPGVLGTLLA GGRVVISGSP APEAAFALME RERVTATSVV
PAIVMRWLQY RDERPGADLG SLELMQVGAS RLEPEVARQV GPKLGCRLQQ VFGMAEGLLC
LTRLDDPDDV VHYTQGRPIS PDDEIRVVDP EGRTVGVGEP GALLTRGPYT PRGYYDSPSA
NARAFTPDGW YRTGDLVRRT PDGNLIVVGR EKDLINRGGE KINAEEVEGF AVQVDGVLQA
AAVGLPDSEL GERICLFVVL ADGTRVELAD VRKVMENAET ASFKLPERLI TLPSLPTTPM
GKIDKKALRA AAGRMSET
