1w76: Difference between revisions
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==About this Structure== | ==About this Structure== | ||
[[1w76]] is a 2 chain structure | [[1w76]] is a 2 chain structure with sequence from [http://en.wikipedia.org/wiki/Torpedo_californica Torpedo californica]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1W76 OCA]. | ||
==See Also== | ==See Also== | ||
Revision as of 01:09, 21 October 2012
ORTHORHOMBIC FORM OF TORPEDO CALIFORNICA ACETYLCHOLINESTERASE (ACHE) COMPLEXED WITH BIS-ACTING GALANTHAMINE DERIVATIVEORTHORHOMBIC FORM OF TORPEDO CALIFORNICA ACETYLCHOLINESTERASE (ACHE) COMPLEXED WITH BIS-ACTING GALANTHAMINE DERIVATIVE
Bifunctional derivatives of the alkaloid galanthamine, designed to interact with both the active site of the enzyme acetylcholinesterase (AChE) and its peripheral cation binding site, have been assayed with Torpedo californica AChE (TcAChE), and the three-dimensional structures of their complexes with the enzyme have been solved by X-ray crystallography. Differences were noted between the IC(50) values obtained for TcAChE and those for Electrophorus electricus AChE. These differences are ascribed to sequence differences in one or two residues lining the active-site gorge of the enzyme. The binding of one of the inhibitors disrupts the native conformation of one wall of the gorge, formed by the loop Trp279-Phe290. It is proposed that flexibility of this loop may permit the binding of inhibitors such as galanthamine, which are too bulky to penetrate the narrow neck of the gorge formed by Tyr121 and Phe330 as seen in the crystal structure.
The complex of a bivalent derivative of galanthamine with torpedo acetylcholinesterase displays drastic deformation of the active-site gorge: implications for structure-based drug design., Greenblatt HM, Guillou C, Guenard D, Argaman A, Botti S, Badet B, Thal C, Silman I, Sussman JL, J Am Chem Soc. 2004 Dec 1;126(47):15405-11. PMID:15563167
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
About this StructureAbout this Structure
1w76 is a 2 chain structure with sequence from Torpedo californica. Full crystallographic information is available from OCA.
See AlsoSee Also
ReferenceReference
- ↑ Greenblatt HM, Guillou C, Guenard D, Argaman A, Botti S, Badet B, Thal C, Silman I, Sussman JL. The complex of a bivalent derivative of galanthamine with torpedo acetylcholinesterase displays drastic deformation of the active-site gorge: implications for structure-based drug design. J Am Chem Soc. 2004 Dec 1;126(47):15405-11. PMID:15563167 doi:http://dx.doi.org/10.1021/ja0466154
- ↑ Mary A, Renko DZ, Guillou C, Thal C. Potent acetylcholinesterase inhibitors: design, synthesis, and structure-activity relationships of bis-interacting ligands in the galanthamine series. Bioorg Med Chem. 1998 Oct;6(10):1835-50. PMID:9839013