MolecularModelingoftheAmino TerminalZincRingDomainofBRCA…氨基末端锌分子模拟研究.pdfVIP

CANCER RESEARCH56. 2539-2545. June I, 19961 Molecular Modeling of the Amino-Terminal Zinc Ring Domain of BRCA1 Rachelle J. Bienstock,1 Tom Darden, Roger Wiseman, Lee Pedersen, and J. Carl Barrett National institute of Environmental Health Sciences, Laboratories of Quantitative and Computational Biology fR. J. B.. T. D., L P.] and Molecular Carcinogenesis IR. W.. J. C. B.J, Research Triangle Park. North Carolina 27709 ABSTRACT in Fig. 1. Although a common functionality for the zinc ring domain has not been identified, it appears to interact with DNA either through The equine herpes virus zinc ring domain nuclear magnetic resonance direct binding or indirectly by mediating protein-protein interactions. structure was used for homology-based modeling of the amino-terminal The zinc ring domain of several proteins has been shown to exhibit zinc ring domain of the BRCA1 breast and ovarian cancer susceptibility gene. The zinc ring domain of BRCAJ is of particular interest because it DNA-binding activity (10) or nuclear localization (11—13). is the location of significant and frequently occurring missense (Cys6tGly, The BRCA1 zinc ring domain and its structure and function are of Cys―Gly,and Cys―Tyr)and frameshift (lSSdelAG) mutations observed