2fy5

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{{STRUCTURE_2fy5| PDB=2fy5 | SCENE= }}
{{STRUCTURE_2fy5| PDB=2fy5 | SCENE= }}
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'''Structures of ligand bound human choline acetyltransferase provide insight into regulation of acetylcholine synthesis'''
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===Structures of ligand bound human choline acetyltransferase provide insight into regulation of acetylcholine synthesis===
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==Overview==
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Choline acetyltransferase (ChAT) catalyzes the synthesis of the neurotransmitter acetylcholine from choline and acetyl-CoA, and its presence is a defining feature of cholinergic neurons. We report the structure of human ChAT to a resolution of 2.2 A along with structures for binary complexes of ChAT with choline, CoA, and a nonhydrolyzable acetyl-CoA analogue, S-(2-oxopropyl)-CoA. The ChAT-choline complex shows which features of choline are important for binding and explains how modifications of the choline trimethylammonium group can be tolerated by the enzyme. A detailed model of the ternary Michaelis complex fully supports the direct transfer of the acetyl group from acetyl-CoA to choline through a mechanism similar to that seen in the serine hydrolases for the formation of an acyl-enzyme intermediate. Domain movements accompany CoA binding, and a surface loop, which is disordered in the unliganded enzyme, becomes localized and binds directly to the phosphates of CoA, stabilizing the complex. Interactions between this surface loop and CoA may function to lower the KM for CoA and could be important for phosphorylation-dependent regulation of ChAT activity.
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{{ABSTRACT_PUBMED_17144655}}
==Disease==
==Disease==
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[[Category: Transferase]]
[[Category: Transferase]]
[[Category: Two domain]]
[[Category: Two domain]]
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''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Sun May 4 04:26:17 2008''
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''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Sun Jul 27 18:00:05 2008''

Revision as of 15:00, 27 July 2008

Image:2fy5.png

Template:STRUCTURE 2fy5

Contents

Structures of ligand bound human choline acetyltransferase provide insight into regulation of acetylcholine synthesis

Template:ABSTRACT PUBMED 17144655

Disease

Known disease associated with this structure: Myasthenic syndrome, congenital, associated with episodic apnea OMIM:[118490]

About this Structure

2FY5 is a Single protein structure of sequence from Homo sapiens. Full crystallographic information is available from OCA.

Reference

Substrate binding and catalytic mechanism of human choline acetyltransferase., Kim AR, Rylett RJ, Shilton BH, Biochemistry. 2006 Dec 12;45(49):14621-31. PMID:17144655

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