HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS		QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

This Article Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Kronman, C. Articles by Shafferman, A. Search for Related Content PubMed PubMed Citation Articles by Kronman, C. Articles by Shafferman, A. Social Bookmarking                      What's this?

J. Biol. Chem., Vol. 269, Issue 45, 27819-27822, 11, 1994

The "back door" hypothesis for product clearance in acetylcholinesterase challenged by site-directed mutagenesis

C Kronman, A Ordentlich, D Barak, B Velan and A Shafferman
Israel Institute for Biological Research, Ness-Ziona.

The active site of acetylcholinesterase is near the bottom of a long and narrow gorge. The dimensions of the gorge and the strong electrostatic field generated by the enzyme appear inconsistent with the enzyme's high turnover rate. Consequently, a "back door" mechanism involving movement of the reaction products through a transient opening near the active center was recently suggested. We investigated this hypothesis in human acetylcholinesterase by testing mutants at key residues (Glu-84, Trp-86, Asp-131, and Val-132) located near or along the putative back door channel. The turnover rates of all mutants tested, and in particular of V132K, where the channel is expected to be sealed by salt bridge Lys-132-Glu-452, are similar to that of the wild type enzyme. This indicates that the proposed back door is not a route for product clearance from the active site gorge of acetylcholinesterase and is probably of no functional relevance to its catalytic activity.
CiteULike    Complore    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this?

This article has been cited by other articles:

				Y. Xu, J.-P. Colletier, M. Weik, H. Jiang, J. Moult, I. Silman, and J. L. Sussman Flexibility of Aromatic Residues in the Active-Site Gorge of Acetylcholinesterase: X-ray versus Molecular Dynamics Biophys. J., September 1, 2008; 95(5): 2500 - 2511. [Abstract] [Full Text] [PDF]

				A. E. Boyd, C. S. Dunlop, L. Wong, Z. Radic, P. Taylor, and D. A. Johnson Nanosecond Dynamics of Acetylcholinesterase Near the Active Center Gorge J. Biol. Chem., June 18, 2004; 279(25): 26612 - 26618. [Abstract] [Full Text] [PDF]

				Y. Bourne, H. C. Kolb, Z. Radic, K. B. Sharpless, P. Taylor, and P. Marchot Freeze-frame inhibitor captures acetylcholinesterase in a unique conformation PNAS, February 10, 2004; 101(6): 1449 - 1454. [Abstract] [Full Text] [PDF]

				S. Simon, A. Le Goff, Y. Frobert, J. Grassi, and J. Massoulie The Binding Sites of Inhibitory Monoclonal Antibodies on Acetylcholinesterase. IDENTIFICATION OF A NOVEL REGULATORY SITE AT THE PUTATIVE "BACK DOOR" J. Biol. Chem., September 24, 1999; 274(39): 27740 - 27746. [Abstract] [Full Text] [PDF]

				A. Ordentlich, D. Barak, C. Kronman, N. Ariel, Y. Segall, B. Velan, and A. Shafferman The Architecture of Human Acetylcholinesterase Active Center Probed by Interactions with Selected Organophosphate Inhibitors J. Biol. Chem., May 17, 1996; 271(20): 11953 - 11962. [Abstract] [Full Text] [PDF]

				A. E. Boyd, A. B. Marnett, L. Wong, and P. Taylor Probing the Active Center Gorge of Acetylcholinesterase by Fluorophores Linked to Substituted Cysteines J. Biol. Chem., July 14, 2000; 275(29): 22401 - 22408. [Abstract] [Full Text] [PDF]