Chemical and mechanistic approaches to the study of protein tyrosine phosphatases.
Protein tyrosine phosphatases (PTPs) are signaling enzymes that control a diverse array of cellular processes. Site-directed mutagenesis, combined with detailed kinetic and mechanistic studies of Yersinia PTP, have contributed greatly to the understanding of the chemical mechanism for PTP catalysis, the nature of the enzymatic transition state, and the means by which the transition state is stabilized. Significant progress has been made in developing specific small-molecule inhibitors as tools to dissect the functional roles of PTP both in normal physiology and pathological conditions. Despite the conserved structural and catalytic properties, recent results show that there are sufficient differences in the PTPs so that potent and selective bidentate inhibitors that simultaneously bind both the active site and a unique adjacent site can be obtained.
Zhang
Zhong-Yin
ZY
Department of Molecular Pharmacology, Albert Einstein College of Medicine, 1300 Morris Park Avenue, Bronx, New York 10461, USA. zyzhang@aecom.yu.edu
D002384:Catalysis; D004791:Enzyme Inhibitors / Q000494:pharmacology; D008958:Models, Molecular; D011487:Protein Conformation; D017027:Protein Tyrosine Phosphatases / Q000037:antagonists & inhibitors / Q000737:chemistry / Q000378:metabolism*; D015398:Signal Transduction
D004791:Enzyme Inhibitors; D017027:Protein Tyrosine Phosphatases