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Neocarzinostatin (NCS) (Mitomalcin) (MMC)

 NCZS_STRCZ              Reviewed;         147 AA.
P0A3R9; P01550;
21-JUL-1986, integrated into UniProtKB/Swiss-Prot.
15-MAR-2005, sequence version 1.
25-OCT-2017, entry version 53.
RecName: Full=Neocarzinostatin;
Short=NCS;
AltName: Full=Mitomalcin;
Short=MMC;
Flags: Precursor;
Name=ncsA;
Streptomyces carzinostaticus.
Bacteria; Actinobacteria; Streptomycetales; Streptomycetaceae;
Streptomyces.
NCBI_TaxID=1897;
[1]
NUCLEOTIDE SEQUENCE [GENOMIC DNA].
STRAIN=ATCC 15944 / E-793 / F-51;
PubMed=8369747; DOI=10.1248/bpb.16.26;
Sakata N., Minamitani S., Kanbe T., Hori M., Hamada M., Edo K.;
"The amino acid sequence of neocarzinostatin apoprotein deduced from
the base sequence of the gene.";
Biol. Pharm. Bull. 16:26-28(1993).
[2]
PROTEIN SEQUENCE OF 35-147.
PubMed=2938543; DOI=10.1016/0003-9861(86)90464-9;
Kuromizu K., Tsunasawa S., Maeda H., Abe O., Sakiyama F.;
"Reexamination of the primary structure of an antitumor protein,
neocarzinostatin.";
Arch. Biochem. Biophys. 246:199-205(1986).
[3]
PRELIMINARY PROTEIN SEQUENCE OF 35-147.
PubMed=6236220;
Gibson B.W., Herlihy W.C., Samy T.S.A., Hahm K.-S., Maeda H.,
Meienhofer J., Biemann K.;
"A revised primary structure for neocarzinostatin based on fast atom
bombardment and gas chromatographic-mass spectrometry.";
J. Biol. Chem. 259:10801-10806(1984).
[4]
STRUCTURE BY NMR, AND PROTEIN SEQUENCE OF 35-147.
PubMed=1831044; DOI=10.1021/bi00245a009;
Gao X., Burkhart W.;
"Two- and three-dimensional proton NMR studies of apo-
neocarzinostatin.";
Biochemistry 30:7730-7739(1991).
[5]
X-RAY CRYSTALLOGRAPHY (1.5 ANGSTROMS).
PubMed=8477746; DOI=10.1111/j.1432-1033.1993.tb17814.x;
Teplyakov A., Obmolova G., Wilson K., Kuromizu K.;
"Crystal structure of apo-neocarzinostatin at 0.15-nm resolution.";
Eur. J. Biochem. 213:737-741(1993).
[6]
X-RAY CRYSTALLOGRAPHY (1.8 ANGSTROMS).
PubMed=8235619; DOI=10.1126/science.8235619;
Kim K.-H., Kwon B.-M., Myers A.G., Rees D.C.;
"Crystal structure of neocarzinostatin, an antitumor protein-
chromophore complex.";
Science 262:1042-1046(1993).
[7]
STRUCTURE BY NMR.
PubMed=1533878; DOI=10.1016/0022-2836(92)91030-S;
Gao X.;
"Three-dimensional solution structure of apo-neocarzinostatin.";
J. Mol. Biol. 225:125-135(1992).
[8]
STRUCTURE BY NMR.
PubMed=2142075; DOI=10.1111/j.1432-1033.1990.tb15571.x;
Adjadj E., Mispelter J., Quiniou E., Dimicoli J.-L., Favaudon V.,
Lhoste J.-M.;
"Proton NMR studies of apo-neocarzinostatin from Streptomyces
carzinostaticus. Sequence-specific assignment and secondary
structure.";
Eur. J. Biochem. 190:263-271(1990).
[9]
STRUCTURE BY NMR.
PubMed=1531194; DOI=10.1111/j.1432-1033.1992.tb16576.x;
Adjadj E., Quiniou E., Mispelter J., Favaudon V., Lhoste J.-M.;
"Three-dimensional solution structure of apo-neocarzinostatin from
Streptomyces carzinostaticus determined by NMR spectroscopy.";
Eur. J. Biochem. 203:505-511(1992).
[10]
STRUCTURE BY NMR.
PubMed=2147566; DOI=10.1021/bi00488a029;
Remerowski M.L., Glaser S.J., Sieker L.C., Samy T.S.A., Drobny G.P.;
"Sequential 1H NMR assignments and secondary structure of
aponeocarzinostatin in solution.";
Biochemistry 29:8401-8409(1990).
[11]
STRUCTURE BY NMR.
PubMed=1834636;
Takashima H., Amiya S., Kobayashi Y.;
"Neocarzinostatin: interaction between the antitumor-active
chromophore and the carrier protein.";
J. Biochem. 109:807-810(1991).
[12]
DISULFIDE BONDS.
PubMed=1832834; DOI=10.1016/0003-9861(91)90081-S;
Kuromizu K., Abe O., Maeda H.;
"Location of the disulfide bonds in the antitumor protein
neocarzinostatin.";
Arch. Biochem. Biophys. 286:569-573(1991).
-!- FUNCTION: NCS has antibiotic activity (for Gram-positive bacteria)
and antitumor activity (for certain mouse tumors). NCS binds non-
covalently to a chromophore which is the cytotoxic and mutagenic
component of the antibiotic. The chromophore binds to DNA as a
weak intercalator and causes single- and double-strand breaks.
-!- SIMILARITY: Belongs to the neocarzinostatin family. {ECO:0000305}.
-----------------------------------------------------------------------
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EMBL; D10996; BAA01764.1; -; Genomic_DNA.
EMBL; S65575; AAB28103.1; -; Genomic_DNA.
PIR; JH0792; ZNSMCC.
PDB; 1J5H; NMR; -; A=35-147.
PDB; 1J5I; NMR; -; A=35-147.
PDB; 1NCO; X-ray; 1.80 A; A/B=35-147.
PDB; 1NOA; X-ray; 1.50 A; A=35-147.
PDB; 1O5P; NMR; -; A=35-147.
PDB; 2CBM; X-ray; 2.03 A; A=35-146.
PDB; 2CBO; X-ray; 1.70 A; A=35-147.
PDB; 2CBQ; X-ray; 2.60 A; A/B/C/D/E/F=35-147.
PDB; 2CBT; X-ray; 2.20 A; A/B=35-146.
PDB; 2G0K; NMR; -; A=35-147.
PDB; 2G0L; NMR; -; A=35-147.
PDBsum; 1J5H; -.
PDBsum; 1J5I; -.
PDBsum; 1NCO; -.
PDBsum; 1NOA; -.
PDBsum; 1O5P; -.
PDBsum; 2CBM; -.
PDBsum; 2CBO; -.
PDBsum; 2CBQ; -.
PDBsum; 2CBT; -.
PDBsum; 2G0K; -.
PDBsum; 2G0L; -.
ProteinModelPortal; P0A3R9; -.
SMR; P0A3R9; -.
DrugBank; DB07776; 2-PHENYL-4H-CHROMEN-4-ONE.
DrugBank; DB08619; TESTOSTERONE HEMISUCCINATE.
EvolutionaryTrace; P0A3R9; -.
GO; GO:0003677; F:DNA binding; IEA:UniProtKB-KW.
GO; GO:0042742; P:defense response to bacterium; IEA:UniProtKB-KW.
Gene3D; 2.60.40.230; -; 1.
InterPro; IPR027273; Neocarzinostatin-like.
InterPro; IPR002186; Neocarzinostatin_fam.
Pfam; PF00960; Neocarzinostat; 1.
PRINTS; PR01885; MACROMOMYCIN.
ProDom; PD012709; NCS-type_chromop; 1.
SUPFAM; SSF49319; SSF49319; 1.
1: Evidence at protein level;
3D-structure; Antibiotic; Antimicrobial; Direct protein sequencing;
Disulfide bond; DNA-binding; Signal.
SIGNAL 1 34 {ECO:0000269|PubMed:1831044,
ECO:0000269|PubMed:2938543}.
CHAIN 35 147 Neocarzinostatin.
/FTId=PRO_0000019461.
DISULFID 71 81 {ECO:0000269|PubMed:1832834}.
DISULFID 122 127 {ECO:0000269|PubMed:1832834}.
CONFLICT 94 94 N -> D (in Ref. 2; AA sequence).
{ECO:0000305}.
STRAND 38 43 {ECO:0000244|PDB:1NOA}.
STRAND 45 47 {ECO:0000244|PDB:2CBO}.
STRAND 52 59 {ECO:0000244|PDB:1NOA}.
STRAND 60 63 {ECO:0000244|PDB:1J5I}.
STRAND 65 75 {ECO:0000244|PDB:1NOA}.
STRAND 78 81 {ECO:0000244|PDB:1NOA}.
HELIX 83 85 {ECO:0000244|PDB:1NOA}.
STRAND 87 90 {ECO:0000244|PDB:1NOA}.
TURN 93 95 {ECO:0000244|PDB:1J5H}.
STRAND 97 102 {ECO:0000244|PDB:1NOA}.
STRAND 105 110 {ECO:0000244|PDB:1NOA}.
STRAND 112 114 {ECO:0000244|PDB:1J5H}.
STRAND 116 121 {ECO:0000244|PDB:1NOA}.
TURN 122 124 {ECO:0000244|PDB:2CBO}.
STRAND 127 132 {ECO:0000244|PDB:1NOA}.
STRAND 134 136 {ECO:0000244|PDB:1J5I}.
STRAND 142 145 {ECO:0000244|PDB:1J5I}.
SEQUENCE 147 AA; 14455 MW; C9BE690CC60AC0C6 CRC64;
MVPISIIRNR VAKVAVGSAA VLGLAVGFQT PAVAAAPTAT VTPSSGLSDG TVVKVAGAGL
QAGTAYDVGQ CAWVDTGVLA CNPADFSSVT ADANGSASTS LTVRRSFEGF LFDGTRWGTV
DCTTAACQVG LSDAAGNGPE GVAISFN


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