Barry Michael Goldstein, M.D., Ph.D.

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The structure of a biologically active molecule (i.e. a drug) is intimately related to its function. Our laboratory employs the technique of macromolecular crystallography to elucidate molecular structure, and to relate this structure to biological function. Crystallographic methods are used to define the structures of complexes between active ligands and their enzymatic targets. This information is used in conjunction with ancillary modeling and computational techniques to identify, at the molecular level, specific interactions important in stabilizing these complexes.

Current research projects examine a series of chemotherapeutic dinucleotide analogues of the cofactor NAD. These agents act as general inhibitors of the class of enzymes known as dehydrogenases. Different inhibitors show marked variations in specificities and affinities for different enzymes. These variations in ligand binding can be attributed to distinct alterations in both intra- and intermolecular interactions observed in the enzyme-inhibitor complexes.

Structural results at atomic resolution are correlated with biochemical and pharmacological data. The ultimate aim of these studies is to identify conformational features which enhance drug activity. These features can then be preserved in the intelligent design of new analogues.

Current Appointments

• Associate Professor - Department of Biochemistry and Biophysics (SMD)
• Associate Professor - Department of Medical Humanities (SMD)

Education
PhD Biophysics	Univ Rochester Sch Med/Dent	1982
MD Medicine	Univ Rochester Sch Med/Dent	1981
MS Biophysics	Univ Rochester Sch Med/Dent	1976
BS Physics	Union College	1973

Lab Website

http://dbb.urmc.rochester.edu/labs/goldstein/

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Recent Journal Articles
Showing the 5 most recent journal articles. (53 available)
Gruswitz F; Frishman M; Goldstein BM; Wedekind JE. "Coupling of MBP fusion protein cleavage with sparse matrix crystallization screens to overcome problematic protein solubility." BioTechniques. 2005; 39(4):476, 478, 480.
Ceccarelli C; Liang ZX; Strickler M; Prehna G; Goldstein BM; Klinman JP; Bahnson BJ. "Crystal structure and amide H/D exchange of binary complexes of alcohol dehydrogenase from Bacillus stearothermophilus: insight into thermostability and cofactor binding." Biochemistry. 2004; 43(18):5266-77.
Nogami K; Wakabayashi H; Ansong C; Fay PJ. "Localization of a pH-dependent, A2 subunit-interactive surface within the factor VIIIa A1 subunit." Biochimica et biophysica acta. 2004; 1701(1-2):25-35.
Strickler M; Goldstein BM; Maxfield K; Shireman L; Kim G; Matteson DS; Jones JP. "Crystallographic studies on the complex behavior of nicotine binding to P450cam (CYP101)." Biochemistry. 2003; 42(41):11943-50.
Pankiewicz KW; Lesiak-Watanabe KB; Watanabe KA; Patterson SE; Jayaram HN; Yalowitz JA; Miller MD; Seidman M; Majumdar A; Prehna G; Goldstein BM. "Novel mycophenolic adenine bis(phosphonate) analogues as potential differentiation agents against human leukemia." Journal of medicinal chemistry. 2002; 45(3):703-12.