1oce

From Proteopedia

Revision as of 14:44, 5 November 2007

ACETYLCHOLINESTERASE (E.C. 3.1.1.7) COMPLEXED WITH MF268

Overview

The crystal structure of Torpedo californica (Tc) acetylcholinesterase, (AChE) carbamoylated by the physostigmine analogue, 8-(cis-2,6-dimethylmorpholino)octylcarbamoyleseroline (MF268) is reported, at 2.7 A resolution. In the X-ray structure, the, dimethylmorpholinooctylcarbamic moiety of MF268 is covalently bound to the, catalytic serine, which is located at the bottom of a long and narrow, gorge. The alkyl chain of the inhibitor fills the upper part of the gorge, blocking the entrance of the active site. This prevents eseroline, the, leaving group of the carbamoylation process, from exiting through this, path. Surprisingly, the relatively bulky eseroline is not found in the, crystal structure, thus implying the existence of an alternative route for, its clearance. This represents indirect evidence that a "back door", opening may occur and shows that the release of products via a "back door", is a likely alternative for this enzyme. However, its relevance as far as, the mechanism of substrate hydrolysis is concerned needs to be, established. This study suggests that the use of properly designed, acylating inhibitors, which can block the entrance of catalytic sites, may, be exploited as a general approach for investigating the existence of, "back doors" for the clearance of products.

About this Structure

1OCE is a Single protein structure of sequence from Torpedo californica with MF2 as ligand. Active as Acetylcholinesterase, with EC number 3.1.1.7 Structure known Active Site: ACT. Full crystallographic information is available from OCA.

Reference

"Back door" opening implied by the crystal structure of a carbamoylated acetylcholinesterase., Bartolucci C, Perola E, Cellai L, Brufani M, Lamba D, Biochemistry. 1999 May 4;38(18):5714-9. PMID:10231521

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