2bag

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[[Image:2bag.gif|left|200px]]
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{{STRUCTURE_2bag| PDB=2bag | SCENE= }}
{{STRUCTURE_2bag| PDB=2bag | SCENE= }}
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'''3D Structure of Torpedo californica acetylcholinesterase complexed with Ganstigmine'''
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===3D Structure of Torpedo californica acetylcholinesterase complexed with Ganstigmine===
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==Overview==
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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.
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The line below this paragraph, {{ABSTRACT_PUBMED_16913695}}, adds the Publication Abstract to the page
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(as it appears on PubMed at http://www.pubmed.gov), where 16913695 is the PubMed ID number.
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{{ABSTRACT_PUBMED_16913695}}
==About this Structure==
==About this Structure==
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==Reference==
==Reference==
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:[http://www.ncbi.nlm.nih.gov/pubmed/16913695 16913695]
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:[http://www.ncbi.nlm.nih.gov/pubmed/16913695 16913695]
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"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:[http://www.ncbi.nlm.nih.gov/pubmed/10231521 10231521]
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Kinetic and structural studies on the interaction of cholinesterases with the anti-Alzheimer drug rivastigmine., Bar-On P, Millard CB, Harel M, Dvir H, Enz A, Sussman JL, Silman I, Biochemistry. 2002 Mar 19;41(11):3555-64. PMID:[http://www.ncbi.nlm.nih.gov/pubmed/11888271 11888271]
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Long chain analogs of physostigmine as potential drugs for Alzheimer's disease: new insights into the mechanism of action in the inhibition of acetylcholinesterase., Perola E, Cellai L, Lamba D, Filocamo L, Brufani M, Biochim Biophys Acta. 1997 Nov 14;1343(1):41-50. PMID:[http://www.ncbi.nlm.nih.gov/pubmed/9428657 9428657]
[[Category: Acetylcholinesterase]]
[[Category: Acetylcholinesterase]]
[[Category: Single protein]]
[[Category: Single protein]]
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[[Category: Neurotransmitter cleavage]]
[[Category: Neurotransmitter cleavage]]
[[Category: Serine hydrolase]]
[[Category: Serine hydrolase]]
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''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Sat May 3 20:02:27 2008''
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''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Tue Jul 29 02:34:19 2008''

Revision as of 23:34, 28 July 2008

Image:2bag.png

Template:STRUCTURE 2bag

3D Structure of Torpedo californica acetylcholinesterase complexed with Ganstigmine

Template:ABSTRACT PUBMED 16913695

About this Structure

2BAG is a Single protein structure of sequence from Torpedo californica. Full crystallographic information is available from OCA.

Reference

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

"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

Kinetic and structural studies on the interaction of cholinesterases with the anti-Alzheimer drug rivastigmine., Bar-On P, Millard CB, Harel M, Dvir H, Enz A, Sussman JL, Silman I, Biochemistry. 2002 Mar 19;41(11):3555-64. PMID:11888271

Long chain analogs of physostigmine as potential drugs for Alzheimer's disease: new insights into the mechanism of action in the inhibition of acetylcholinesterase., Perola E, Cellai L, Lamba D, Filocamo L, Brufani M, Biochim Biophys Acta. 1997 Nov 14;1343(1):41-50. PMID:9428657

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