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{{STRUCTURE_1f8u| PDB=1f8u | SCENE= }} | |||
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'''CRYSTAL STRUCTURE OF MUTANT E202Q OF HUMAN ACETYLCHOLINESTERASE COMPLEXED WITH GREEN MAMBA VENOM PEPTIDE FASCICULIN-II''' | '''CRYSTAL STRUCTURE OF MUTANT E202Q OF HUMAN ACETYLCHOLINESTERASE COMPLEXED WITH GREEN MAMBA VENOM PEPTIDE FASCICULIN-II''' | ||
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[[Category: Silman, I.]] | [[Category: Silman, I.]] | ||
[[Category: Sussman, J L.]] | [[Category: Sussman, J L.]] | ||
[[Category: | [[Category: Human acetylcholinesterase]] | ||
[[Category: | [[Category: Hydrolase]] | ||
[[Category: | [[Category: Hydrolase/hydrolase inhibitor]] | ||
[[Category: | [[Category: Serine esterase]] | ||
[[Category: | [[Category: Snake toxin]] | ||
''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Fri May 2 16:02:24 2008'' | |||
''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on | |||
Revision as of 16:02, 2 May 2008
CRYSTAL STRUCTURE OF MUTANT E202Q OF HUMAN ACETYLCHOLINESTERASE COMPLEXED WITH GREEN MAMBA VENOM PEPTIDE FASCICULIN-II
OverviewOverview
Structures of recombinant wild-type human acetylcholinesterase and of its E202Q mutant as complexes with fasciculin-II, a 'three-finger' polypeptide toxin purified from the venom of the eastern green mamba (Dendroaspis angusticeps), are reported. The structure of the complex of the wild-type enzyme was solved to 2.8 A resolution by molecular replacement starting from the structure of the complex of Torpedo californica acetylcholinesterase with fasciculin-II and verified by starting from a similar complex with mouse acetylcholinesterase. The overall structure is surprisingly similar to that of the T. californica enzyme with fasciculin-II and, as expected, to that of the mouse acetylcholinesterase complex. The structure of the E202Q mutant complex was refined starting from the corresponding wild-type human acetylcholinesterase structure, using the 2.7 A resolution data set collected. Comparison of the two structures shows that removal of the charged group from the protein core and its substitution by a neutral isosteric moiety does not disrupt the functional architecture of the active centre. One of the elements of this architecture is thought to be a hydrogen-bond network including residues Glu202, Glu450, Tyr133 and two bridging molecules of water, which is conserved in other vertebrate acetylcholinesterases as well as in the human enzyme. The present findings are consistent with the notion that the main role of this network is the proper positioning of the Glu202 carboxylate relative to the catalytic triad, thus defining its functional role in the interaction of acetylcholinesterase with substrates and inhibitors.
DiseaseDisease
Known disease associated with this structure: Blood group, Yt system OMIM:[100740]
About this StructureAbout this Structure
1F8U is a Protein complex structure of sequences from Dendroaspis angusticeps and Homo sapiens. Full crystallographic information is available from OCA.
ReferenceReference
Structures of recombinant native and E202Q mutant human acetylcholinesterase complexed with the snake-venom toxin fasciculin-II., Kryger G, Harel M, Giles K, Toker L, Velan B, Lazar A, Kronman C, Barak D, Ariel N, Shafferman A, Silman I, Sussman JL, Acta Crystallogr D Biol Crystallogr. 2000 Nov;56(Pt 11):1385-94. PMID:11053835 Page seeded by OCA on Fri May 2 16:02:24 2008