1ayu
From Proteopedia
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'''CRYSTAL STRUCTURE OF CYSTEINE PROTEASE HUMAN CATHEPSIN K IN COMPLEX WITH A COVALENT SYMMETRIC BISCARBOHYDRAZIDE INHIBITOR''' | '''CRYSTAL STRUCTURE OF CYSTEINE PROTEASE HUMAN CATHEPSIN K IN COMPLEX WITH A COVALENT SYMMETRIC BISCARBOHYDRAZIDE INHIBITOR''' | ||
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[[Category: Smith, W W.]] | [[Category: Smith, W W.]] | ||
[[Category: Zhao, B.]] | [[Category: Zhao, B.]] | ||
| - | [[Category: | + | [[Category: Hydrolase]] |
| - | [[Category: | + | [[Category: Sulfhydryl proteinase]] |
| - | + | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Fri May 2 10:51:30 2008'' | |
| - | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on | + | |
Revision as of 07:51, 2 May 2008
CRYSTAL STRUCTURE OF CYSTEINE PROTEASE HUMAN CATHEPSIN K IN COMPLEX WITH A COVALENT SYMMETRIC BISCARBOHYDRAZIDE INHIBITOR
Overview
Potent and selective active-site-spanning inhibitors have been designed for cathepsin K, a cysteine protease unique to osteoclasts. They act by mechanisms that involve tight binding intermediates, potentially on a hydrolytic pathway. X-ray crystallographic, MS, NMR spectroscopic, and kinetic studies of the mechanisms of inhibition indicate that different intermediates or transition states are being represented that are dependent on the conditions of measurement and the specific groups flanking the carbonyl in the inhibitor. The species observed crystallographically are most consistent with tetrahedral intermediates that may be close approximations of those that occur during substrate hydrolysis. Initial kinetic studies suggest the possibility of irreversible and reversible active-site modification. Representative inhibitors have demonstrated antiresorptive activity both in vitro and in vivo and therefore are promising leads for therapeutic agents for the treatment of osteoporosis. Expansion of these inhibitor concepts can be envisioned for the many other cysteine proteases implicated for therapeutic intervention.
About this Structure
1AYU is a Single protein structure of sequence from Homo sapiens. Full crystallographic information is available from OCA.
Reference
Design of potent and selective human cathepsin K inhibitors that span the active site., Thompson SK, Halbert SM, Bossard MJ, Tomaszek TA, Levy MA, Zhao B, Smith WW, Abdel-Meguid SS, Janson CA, D'Alessio KJ, McQueney MS, Amegadzie BY, Hanning CR, DesJarlais RL, Briand J, Sarkar SK, Huddleston MJ, Ijames CF, Carr SA, Garnes KT, Shu A, Heys JR, Bradbeer J, Zembryki D, Lee-Rykaczewski L, James IE, Lark MW, Drake FH, Gowen M, Gleason JG, Veber DF, Proc Natl Acad Sci U S A. 1997 Dec 23;94(26):14249-54. PMID:9405598 Page seeded by OCA on Fri May 2 10:51:30 2008
