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

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

Contact Information

University of Rochester Medical Center
School of Medicine and Dentistry
601 Elmwood Ave, Box 712
Rochester, NY 14642

Office: (585) 275-5095
Fax: (585) 275-6007

Research Bio

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.

Recent Journal Articles

Showing the 5 most recent journal articles. 53 available »

2005 Oct
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 Oct; 39(4):476, 478, 480.
2004 Sep 1
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 Sep 1; 1701(1-2):25-35.
2004 May 11
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 May 11; 43(18):5266-77.
2003 Oct 21
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 Oct 21; 42(41):11943-50.
2002 Apr
Pankiewicz KW, Watanabe KA, Lesiak-Watanabe K, Goldstein BM, Jayaram HN. "The chemistry of nicotinamide adenine dinucleotide (NAD) analogues containing C-nucleosides related to nicotinamide riboside." Current medicinal chemistry. 2002 Apr; 9(7):733-41.

Current Appointments

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

Education

PhD | Biophysics | Univ Rochester Sch Med/Dent1982
MD | Medicine | Univ Rochester Sch Med/Dent1981
MS | Biophysics | Univ Rochester Sch Med/Dent1976
BS | Physics | Union College1973