This Article Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Services Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Bienstock, R. J. Articles by Barrett, J. C. Search for Related Content PubMed PubMed Citation Articles by Bienstock, R. J. Articles by Barrett, J. C.

Molecular Modeling of the Amino-Terminal Zinc Ring Domain of BRCA1

National Institute of Environmental Health Sciences, Laboratories of Quantitative and Computational Biology [R. J. B., T. D., L. P.] and Molecular Carcinogenesis [R. W., J. C. B.], Research Triangle Park, North Carolina 27709

The equine herpes virus zinc ring domain nuclear magnetic resonance structure was used for homology-based modeling of the amino-terminal zinc ring domain of the BRCA1 breast and ovarian cancer susceptibility gene. The zinc ring domain of BRCA1 is of particular interest because it is the location of significant and frequently occurring missense (Cys⁶¹Gly, Cys⁶⁴Gly, and Cys⁶⁴Tyr) and frameshift (185delAG) mutations observed in several high-risk kindreds. The BRCA1 zinc ring domain possesses 54% sequence similarity with the equine herpes virus zinc ring domain. The model structure undergoes little conformational variance after 140 ps of solvated molecular dynamics. This model proposes BRCA1 zinc ring domain residues that may play a role in DNA binding and/or protein-protein interactions. These predictions provide a point of departure for the design of mutants to probe BRCA1 zinc ring domain functionality.

¹ To whom requests for reprints should be addressed, at National Institute of Environmental Health Sciences, P.O. Box 12233, Mail Drop 10-03, Research Triangle Park, NC 27709. Phone: (919) 541-3397; Fax: (919) 541-1578; E-mail: rachelle@picard.niehs.nih.gov.

Received 12/28/95. Accepted 4/ 3/96.

This article has been cited by other articles:

				M. E. Thompson, C. L. Robinson-Benion, and J. T. Holt An Amino-terminal Motif Functions as a Second Nuclear Export Sequence in BRCA1 J. Biol. Chem., June 10, 2005; 280(23): 21854 - 21857. [Abstract] [Full Text] [PDF]

				C. Osborne, P. Wilson, and D. Tripathy Oncogenes and Tumor Suppressor Genes in Breast Cancer: Potential Diagnostic and Therapeutic Applications Oncologist, July 1, 2004; 9(4): 361 - 377. [Abstract] [Full Text] [PDF]

				D. Thompson and D. Easton Variation in BRCA1 Cancer Risks by Mutation Position Cancer Epidemiol. Biomarkers Prev., April 1, 2002; 11(4): 329 - 336. [Abstract] [Full Text] [PDF]

				T.-C. Suen and P. E. Goss Transcription of BRCA1 Is Dependent on the Formation of a Specific Protein-DNA Complex on the Minimal BRCA1 Bi-directional Promoter J. Biol. Chem., October 29, 1999; 274(44): 31297 - 31304. [Abstract] [Full Text] [PDF]

				C. WIDMANN, S. GIBSON, M. B. JARPE, and G. L. JOHNSON Mitogen-Activated Protein Kinase: Conservation of a Three-Kinase Module From Yeast to Human Physiol Rev, January 1, 1999; 79(1): 143 - 180. [Abstract] [Full Text] [PDF]

				S. J. Dowell, A. L. Bishop, S. L. Dyos, A. J. Brown, and M. S. Whiteway Mapping of a Yeast G Protein ß{gamma} Signaling Interaction Genetics, December 1, 1998; 150(4): 1407 - 1417. [Abstract] [Full Text]

				C. Inouye, N. Dhillon, and J. Thorner Ste5 RING-H2 Domain: Role in Ste4-Promoted Oligomerization for Yeast Pheromone Signaling Science, October 3, 1997; 278(5335): 103 - 106. [Abstract] [Full Text]