The Zinc-Dependent Protease Activity of the Botulinum Neurotoxins 英文参考文献.docVIP

Toxins 2010, 2, 978-997; doi:10.3390/toxins2050978 OPEN ACCESS toxins ISSN 2072-6651 /journal/toxins Review The Zinc-Dependent Protease Activity of the Botulinum Neurotoxins Frank J. Lebeda 1,*, Regina Z. Cer 2, Uma Mudunuri 2, Robert Stephens 2, Bal Ram Singh 3 and Michael Adler 4 1 US Army Medical Research and Materiel Command, Ft. Detrick, MD 21702-5012, USA 2 Bioinformatics Support Group, Advanced Biomedical Computing Center, Information Systems Program, SAIC-Frederick Inc., NCI-Frederick, Frederick, MD 21702, USA; E-Mails: cerr@ (R.Z.C.); mudunuriu@ (U.M.); stephensr@ (R.S.) 3 Botulinum Research Center, University of Massachusetts Dartmouth, 285 Old Westport Road, Dartmouth, MA 02747, USA; E-Mail: bsingh@ (B.R.S.) 4 US Army Medical Research Institute of Chemical Defense, Aberdeen Proving Ground, MD 21010- 5400, USA; E-Mail: michael.adler@ (M.A.) * Author to whom correspondence should be addressed; E-Mail: frank.lebeda@; Tel.: 1-301-629-7569; Fax: 1-301-619-7067. Received: 1 April 2010; in revised form: 30 April 2010 / Accepted: 5 May 2010 / Published: 7 May 2010 Abstract: The botulinum neurotoxins (BoNT, serotypes A-G) are some of the most toxic proteins known and are the causative agents of botulism. Following exposure, the neurotoxin binds and enters peripheral cholinergic nerve endings and specifically and selectively cleaves one or more SNARE proteins to produce flaccid paralysis. This review centers on the kinetics of the Zn-dependent proteolytic activities of these neurotoxins, and briefly describes inhibitors, activators and factors underlying persistence of toxin action. Some of the structural, enzymatic and inhibitor data that are discussed here are available at the botulinum neurotoxin resource, BotDB (). Keywords: catalysis; energy; kcat; Km; superactivation  Toxins 2010, 2 979 1. Introduction This review focuses on the enzymatic function, thermodynamic properties and susceptibility