2bag: Difference between revisions
New page: left|200px<br /> <applet load="2bag" size="450" color="white" frame="true" align="right" spinBox="true" caption="2bag, resolution 2.40Å" /> '''3D Structure of Tor... |
No edit summary |
||
| Line 1: | Line 1: | ||
[[Image:2bag.gif|left|200px]]<br /> | [[Image:2bag.gif|left|200px]]<br /><applet load="2bag" size="350" color="white" frame="true" align="right" spinBox="true" | ||
<applet load="2bag" size=" | |||
caption="2bag, resolution 2.40Å" /> | caption="2bag, resolution 2.40Å" /> | ||
'''3D Structure of Torpedo californica acetylcholinesterase complexed with Ganstigmine'''<br /> | '''3D Structure of Torpedo californica acetylcholinesterase complexed with Ganstigmine'''<br /> | ||
| Line 8: | Line 7: | ||
==About this Structure== | ==About this Structure== | ||
2BAG is a [http://en.wikipedia.org/wiki/Single_protein Single protein] structure of sequence from [http://en.wikipedia.org/wiki/Torpedo_californica Torpedo californica] with NAG, 1PE, GSG and MES as [http://en.wikipedia.org/wiki/ligands ligands]. Active as [http://en.wikipedia.org/wiki/Acetylcholinesterase Acetylcholinesterase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=3.1.1.7 3.1.1.7] Full crystallographic information is available from [http:// | 2BAG is a [http://en.wikipedia.org/wiki/Single_protein Single protein] structure of sequence from [http://en.wikipedia.org/wiki/Torpedo_californica Torpedo californica] with <scene name='pdbligand=NAG:'>NAG</scene>, <scene name='pdbligand=1PE:'>1PE</scene>, <scene name='pdbligand=GSG:'>GSG</scene> and <scene name='pdbligand=MES:'>MES</scene> as [http://en.wikipedia.org/wiki/ligands ligands]. Active as [http://en.wikipedia.org/wiki/Acetylcholinesterase Acetylcholinesterase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=3.1.1.7 3.1.1.7] Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2BAG OCA]. | ||
==Reference== | ==Reference== | ||
| Line 30: | Line 29: | ||
[[Category: serine hydrolase]] | [[Category: serine hydrolase]] | ||
''Page seeded by [http:// | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Fri Feb 15 17:15:40 2008'' | ||
Revision as of 18:15, 15 February 2008
|
3D Structure of Torpedo californica acetylcholinesterase complexed with Ganstigmine
OverviewOverview
Ganstigmine is an orally active, geneserine derived, carbamate-based, acetylcholinesterase inhibitor developed for the treatment of Alzheimer's, disease. The crystal structure of the ganstigmine conjugate with Torpedo, californica acetylcholinesterase (TcAChE) has been determined at 2.40 A, resolution, and a detailed structure-based analysis of the in vitro and ex, vivo anti-AChE activity by ganstigmine and by new geneserine derivatives, is presented. The carbamoyl moiety is covalently bound to the active-site, serine, whereas the leaving group geneseroline is not retained in the, catalytic pocket. The nitrogen atom of the carbamoyl moiety of ganstigmine, is engaged in a key hydrogen-bonding interaction with the active site, histidine (His440). This result offers an explanation for the inactivation, of the catalytic triad and may account for the long duration of action of, ganstigmine in vivo. The 3D structure also provides a structural framework, for the design of compounds with improved binding affinity and, pharmacological properties.
About this StructureAbout this Structure
2BAG is a Single protein structure of sequence from Torpedo californica with , , and as ligands. Active as Acetylcholinesterase, with EC number 3.1.1.7 Full crystallographic information is available from OCA.
ReferenceReference
Structural determinants of Torpedo californica acetylcholinesterase inhibition by the novel and orally active carbamate based anti-alzheimer drug ganstigmine (CHF-2819)., Bartolucci C, Siotto M, Ghidini E, Amari G, Bolzoni PT, Racchi M, Villetti G, Delcanale M, Lamba D, J Med Chem. 2006 Aug 24;49(17):5051-8. PMID:16913695
Page seeded by OCA on Fri Feb 15 17:15:40 2008