Michael W. Crowder
Metalloenzymes, antibiotic resistance, metal ion homeostasis, inhibitor design
My research interests involve the mechanistic and structural characterization of metalloenzymes using spectroscopic, molecular biological, and kinetic techniques. The enzyme systems under study are biomedically relevant; the ultimate goal is the rational design and preparation of clinically useful inhibitors. We are taking a multidisciplinary approach, using bioinorganic, bioorganic, and physical studies to develop a compound that will specifically inhibit metallo-ß-lactamases. These enzymes destroy penicillins and cephalosporins. A second project deals with understanding Zn(II) homeostasis in bacteria. Specifically, we are conducting experiments to understand how Zn(II) is transported in E. coli.
1. J. A. Easton, P. Thompson, and M. W. Crowder, “Time-Dependent Translational Response to E. coli to Excess Zn(II)”, J. Biomol. Tech., 17, 303-307 (2006).
2. A. L. Costello, N. P. Sharma, K. W. Yang, M. W. Crowder, and D. L. Tierney, “EXAFS of the Zinc Binding Sites in the Class B2 Metallo-β-Lactamase ImiS from Aeromonas veronii bv. sobria”, Biochemistry, 45, 13650-13658 (2006).
3. M. L. Matthews, G. Periyannan, T. K. Sigdel, C. Hajdin, B. Bennett, and M. W. Crowder, “Probing the Reaction Mechanism of the D-ala-D-ala Dipeptidase, VanX, by Using Stopped-Flow Kinetic and Rapid-Freeze Quench EPR Studies on the Co(II)-Substituted Enzyme”, J. Am. Chem. Soc., 128, 13050-13051 (2006).
4. Q. Sun, A. Law, M. W. Crowder, and H. M. Geysen, “Homo-Cysteinyl Peptide Inhibitors of the L1 Metallo-β-Lactamase, and SAR as Determined by Combinatorial Library Synthesis”, Bioorg. Med. Chem. Lett., 16, 5169-5175 (2006).
5. N. P. Sharma, C. Hajdin, S. Chandrasekar, B. Bennett, and M. W. Crowder, “Mechanistic Studies on the Mononuclear Zn(II)-Containing Metallo-β-Lactamase ImiS from Aeromonas sobria”, Biochemistry, 45, 10729-10738 (2006).
6. T. K. Sigdel, J. A. Easton, and M. W. Crowder, “Transcriptional Response of E. coli to TPEN”, J. Bacteriol., 188, 6709-6713 (2006)
7. M. W. Crowder, J. Spencer, and A. Vila, “Metallo-β-Lactamases: Novel Weaponry for Antibiotic Resistance in Bacteria”, Acc. Chem. Res., 39, 721-728 (2006).
8. M. W. Crowder, “Combating Vancomyin Resistance in Bacteria: Targeting the D-ala-D-ala Dipeptidase VanX”, Curr. Drug Targets – Infect. Disorders, 6(2), 147-158 (2006).
9. A. L. Costello, G. Periyannan, K.-W. Yang, M. W. Crowder, and D. L. Tierney, “Site Selective Binding of Zn(II) to Metallo-β-Lactamase L1 from Stenotrophomonas maltophilia”, J. Biol. Inorg. Chem., 11, 351-358 (2006).
10. T. K. Sigdel, R. Cilliers, P. R. Gursahaney, P. Thompson, J. A. Easton, and M. W. Crowder, “Proteomic Analysis of Zn(II) Responsive Proteins in E. coli”, Biometals, 19, 461-471 (2006).
11. F. C. Golich, M. Han, and M. W. Crowder, “Over-expression, Purification, and Characterization of Aminopeptidase N (PepN) from Escherichia coli”, Prot. Express. Purif., 47, 634-639 (2006).
12. G. R. Periyannan, A. L. Costello, D. L. Tierney, B. Bennett, K. W. Yang, and M. W. Crowder, “Sequential Binding of Co(II) to Metallo-β-Lactamase CcrA”, Biochemistry, 45, 1313-1320 (2006).
13. J.D. Garrity, B. Bennett, and M.W. Crowder, "Direct Evidence that Reaction Intermediate in Metallo-b-lactamase L1 is Metal Bound" Biochemistry (2005) 44 1078-1087.
14. R.M. Breece, A. Costello, B. Bennett, T.K. Sigdel, M.L. Matthews, D.L. Tierney, and M.W. Crowder, "A five-coordinate metal center in Co(II)-substituted VanX" J. Biol. Chem. (2005) 280 11074-11081.
15. P.A. Crawford, K.W. Yang, N. Sharma, B. Bennett, and M.W. Crowder "Spectroscopic Studies on Co(II)-Substituted Metallo-b-Lactamase ImiS from Aeromonas veronii bv. sobria" Biochemistry (2005) 44 5168 - 5176.
16. Ke-Wu Yang, F.C. Golich, T.K. Sigdel, and M.W. Crowder, "Phosphinate, Sulfonate, and Sulfonamidate Dipeptides as Potential Inhibitors of E. coli Aminopeptidase N" Bioorg. Med. Chem. Lett. (2005) 15 5150 - 5153.
17. G.P.K. Marasinghe, I.M. Sander, Brian Bennett, Ke-Wu Yang, Gopalraj Periyannan, C.A. Makaroff, and M.W. Crowder, "Structural Studies on a Mitochondrial Glyoxalase II" J. Biol. Chem. (2005) 280 40668-40675.