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Science 12 November 1993:
Vol. 262. no. 5136, pp. 1042 - 1046
DOI: 10.1126/science.8235619
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Articles

Science, Vol 262, Issue 5136, 1042-1046
Copyright © 1993 by American Association for the Advancement of Science

articles

Crystal structure of neocarzinostatin, an antitumor protein-chromophore complex

KH Kim, BM Kwon, AG Myers, and DC Rees

Division of Chemistry and Chemical Engineering, California Institute of Technology, Pasadena 91125.

Structures of the protein-chromophore complex and the apoprotein form of neocarzinostatin were determined at 1.8 angstrom resolution. Neocarzinostatin is composed of a labile chromophore with DNA-cleaving activity and a stabilizing protein. The chromophore displays marked nonlinearity of the triple bonds and is bound noncovalently in a pocket formed by the two protein domains. The chromophore pi-face interacts with the phenyl ring edges of Phe52 and Phe78. The amino sugar and carbonate groups of the chromophore are solvent exposed, whereas the epoxide, acetylene groups, and carbon C-12, the site of nucleophilic thiol addition during chromophore activation, are unexposed. The position of the amino group of the chromophore carbohydrate relative to C-12 supports the idea that the amino group plays a role in thiol activation.


THIS ARTICLE HAS BEEN CITED BY OTHER ARTICLES:
A New Model for Ligand Release: ROLE OF SIDE CHAIN IN GATING THE ENEDIYNE ANTIBIOTIC.
P. Hariharan, W. Liang, S.-H. Chou, and D.-H. Chin (2006)
J. Biol. Chem. 281, 16025-16033
   Abstract »    Full Text »    PDF »
Role of the tyrosine corner motif in the stability of neocarzinostatin.
M. Nicaise, M. Valerio-Lepiniec, N. Izadi-pruneyre, E. Adjadj, P. Minard, and M. Desmadril (2003)
Protein Eng. Des. Sel. 16, 733-738
   Abstract »    Full Text »    PDF »
Reinvestigation of the Proteolytic Activity of Neocarzinostatin.
B. Heyd, G. Lerat, E. Adjadj, P. Minard, and M. Desmadril (2000)
J. Bacteriol. 182, 1812-1818
   Abstract »    Full Text »
Release of the Neocarzinostatin Chromophore from the Holoprotein Does Not Require Major Conformational Change of the Tertiary and Secondary Structures Induced by Trifluoroethanol.
G. Christopher, P. Sudhahar, K. Balamurugan, and D.-H. Chin (2000)
J. Biol. Chem. 275, 39900-39906
   Abstract »    Full Text »    PDF »
Gene transcription analysis of Saccharomyces cerevisiae exposed to neocarzinostatin protein- chromophore complex reveals evidence of DNA damage, a potential mechanism of resistance, and consequences of prolonged exposure.
S. E. Schaus, D. Cavalieri, and A. G. Myers (2001)
PNAS 98, 11075-11080
   Abstract »    Full Text »    PDF »


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Science. ISSN 0036-8075 (print), 1095-9203 (online)