skip to content
Adjunct Professor Sydney P. Craig III
picture Adjunct Professor Sydney P. Craig III
University of Connecticut
Department of Molecular and Cell Biology
91 North Eagleville Road, Unit 3125
Storrs, CT 06269-3125

Telephone:
Fax: (860) 486-4331
E-Mail: sydney.craig@uconn.edu

Education: 1970 Ph.D. in Developmental Biology & Genetics from Caltech

Research Interests: Protein Biochemistry; Protein Structure/Function Relationships; Molecular Biology; and Enzyme Structure Based Drug Design.

Since 1986 Syd Craig has been investigating hypoxanthine phosphoribosyltransferases (HPRTs) as possible targets for drugs in the treatment of diseases such as malaria, schistosomiasis, and American trypanosomiasis. Our solution of the 3-D structure for a closed conformation of the HPRT from Trypanosoma cruzi (Focia et al., 1998b) enabled us to use computational methods to efficiently identify compounds that bind to the active sites of HPRTs. Several of these compounds have been shown also to inhibit the growth of parasites in infected mammalian cells (Freymann et al., 2000). Analyses of interactions between HPRTs and the inhibitors are underway and the results of these studies will be used to guide modifications of the compounds in future efforts to optimize binding interactions and improve pharmacological properties.

Selected Publications:
Fernandez, D., Wenck, M.A., Craig, S.P. III and Delfino, J.M. (2004) The purine transferase from Trypanosoma cruzi as a potential target for bisphosphonate-based chemotherapeutic compounds. Bioorg. & Med. Chem. Letters 14, 4501-4504.

Wenck, M.A., Medrano, F.J., Eakin, A.E. and Craig, S.P. III (2004) Steady-state kinetics of the hypoxanthine phosphoribosyltransferase from Trypanosoma cruzi. Biochimica et Biophysica Acta 1700, 11-18.

Butterworth, A.C., Medrano, F.J., Eakin, A.E. and Craig, S.P. III (2004) Saturation mutagenesis, complement selection, and steady-state kinetics studies illuminate the functional roles of invariant residues in active site loop I of the hypoxanthine phosphoribosyltransferase from Trypanosoma cruzi. Biochimica et Biophysica Acta 1699, 87-94.

Canyuk, B., Medrano, F.J., Wenck, M.A., Focia, P.J., Eakin, A.E. and Craig, S.P. III (2004) Interactions at the dimer interface influence the relative efficiencies for nucleotide synthesis and pyrophosphorolysis in a phosphoribosyltransferase. Journal of Molecular Biology 335, 905-921.

Medrano, F.J., Wenck, M.A., Eakin, A.E. and Craig, S.P. III (2003) Functional roles for amino acids in active site loop II of a hypoxanthine phosphoribosyltransferase. Biochimica et Biophysica Acta 1650, 105-116.

Medrano, F.J., Wenck, M.A., Engel, J.C. and Craig, S.P. III (2003) Analysis of 6-(2,2-dichloroacetamido)chrysene interaction with the hypoxanthine phosphoribosyltransferase from Trypanosoma cruzi. Journal of Medicinal Chemistry 46, 2548-2550.

Lee, C.C., Medrano, F.J., Craig, S.P. and Eakin, A.E. (2001) Investigation of the functional role of active site loop II in a hypoxanthine phosphoribosyltransferase. Biochimica et Biophysica Acta 1537, 63-70.

Freymann, D.M., Wenck, M.A., Engel, J.C., Feng, J., Focia, P.J., Eakin, A.E. and Craig, S.P. III (2000) Efficient identification of inhibitors targeting the closed active site conformation of the HPRT from Trypanosoma cruzi. Chemistry & Biology 7, 957-968.

Craig, S.P. III and Eakin, A.E. (2000) Purine phosphoribosyltransferases.  Journal of Biological Chemistry 275, 20231-20234.

Focia, P.J., Craig, S.P. III, and Eakin, A.E. (1998b) Approaching the transition state in the crystal structure of a phosphoribosyltransferase. Biochemistry 37, 17120-17127.

Nieves-Alicea, R., Focia, P.J., Craig, S.P III, and Eakin, A.E. (1998) Limited proteolysis of a trypanosomal phosphoribosyltransferase yields crystals that diffract X-rays to near atomic resolution. Biochimica et Biophysica Acta 1388, 500-505.

Focia, P.J., Craig, S.P. III, Nieves-Alicea, R., Fletterick R. J., and Eakin, A.E. (1998a) A 1.4 Å crystal structure for the hypoxanthine phosphoribosyltransferase of Trypanosoma cruzi. Biochemistry 37, 15066-15077.

Lee, C.C., Craig, S.P. III, and Eakin, A.E. (1998) A single amino acid substitution in the human and a bacterial hypoxanthine phosphoribosyltransferase modulates specificity for the binding of guanine. Biochemistry 37, 3491-3498.

Eakin, A.E., Guerra, A., Focia, P.J., Torres-Martinez, J., and Craig, S.P. III (1997) Hypoxanthine phosphoribosyltransferase from Trypanosoma cruzi as a target for structure-based inhibitor design: Crystallization and inhibition studies with purine analogs. Antimicrobial Agents & Chemotherapy 41, 1686-1692.

Craig, S.P .III and Eakin, A.E. (1997) Purine salvage enzymes of parasites as targets for structure based inhibitor design. Parasitology Today 13, 238-241.