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Minerva Biotecnologica 2007 December;19(4):139-50

Copyright © 2007 EDIZIONI MINERVA MEDICA

lingua: Inglese

Molecular recognition of thermolysin and homologous zinc-metalloproteinases

Khan* M. T. H., Yimingjiang W., Sylte I.

School of Molecular and Structural Biology Institute of Medical Biology Department of Pharmacology Faculty of Medicine, University of Tromsø, Tromsø, Norway

Thermolysin is a thermostable zinc-metalloproteinase secreted by Bacillus thermoproteolyticus and the prototype enzyme of the M4 family of proteinases, which at present consists of 293 family members. These proteinases are secreted from several hundreds of organism and cause lethal infections to mankind. Thermolysin is an attractive target for protein engineering experiments to understand the catalytic mechanism, thermostability, and halophilicity. Thermolysin is very similar in overall structure and active site geometry to angiotensin converting enzyme (ACE) and neprilysin. Thermolysin inhibitors are therefore potential ACE and neprilysin inhibitors and candidates for developing antihypertensive drugs. This paper is a critical review of structural and functional aspects of thermolysin and homologous proteins, and of the present knowledge about thermolysin inhibitors.