1wci

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[[Image:1wci.gif|left|200px]]
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{{STRUCTURE_1wci| PDB=1wci | SCENE= }}
{{STRUCTURE_1wci| PDB=1wci | SCENE= }}
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'''REACTIVITY MODULATION OF HUMAN BRANCHED-CHAIN ALPHA-KETOACID DEHYDROGENASE BY AN INTERNAL MOLECULAR SWITCH'''
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===REACTIVITY MODULATION OF HUMAN BRANCHED-CHAIN ALPHA-KETOACID DEHYDROGENASE BY AN INTERNAL MOLECULAR SWITCH===
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==Overview==
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The dehydrogenase/decarboxylase (E1b) component of the 4 MD human branched-chain alpha-ketoacid dehydrogenase complex (BCKDC) is a thiamin diphosphate (ThDP)-dependent enzyme. We have determined the crystal structures of E1b with ThDP bound intermediates after decarboxylation of alpha-ketoacids. We show that a key tyrosine residue in the E1b active site functions as a conformational switch to reduce the reactivity of the ThDP cofactor through interactions with its thiazolium ring. The intermediates do not assume the often-postulated enamine state, but likely a carbanion state. The carbanion presumably facilitates the second E1b-catalyzed reaction, involving the transfer of an acyl moiety from the intermediate to a lipoic acid prosthetic group in the transacylase (E2b) component of the BCKDC. The tyrosine switch further remodels an E1b loop region to promote E1b binding to E2b. Our results illustrate the versatility of the tyrosine switch in coordinating the catalytic events in E1b by modulating the reactivity of reaction intermediates.
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(as it appears on PubMed at http://www.pubmed.gov), where 16472748 is the PubMed ID number.
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{{ABSTRACT_PUBMED_16472748}}
==About this Structure==
==About this Structure==
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[[Category: Thiamine]]
[[Category: Thiamine]]
[[Category: Thiamine diphosphate]]
[[Category: Thiamine diphosphate]]
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''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Sat May 3 13:27:53 2008''
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''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Tue Jul 29 09:28:26 2008''

Revision as of 06:28, 29 July 2008

Image:1wci.png

Template:STRUCTURE 1wci

REACTIVITY MODULATION OF HUMAN BRANCHED-CHAIN ALPHA-KETOACID DEHYDROGENASE BY AN INTERNAL MOLECULAR SWITCH

Template:ABSTRACT PUBMED 16472748

About this Structure

1WCI is a Protein complex structure of sequences from Homo sapiens. Full crystallographic information is available from OCA.

Reference

A versatile conformational switch regulates reactivity in human branched-chain alpha-ketoacid dehydrogenase., Machius M, Wynn RM, Chuang JL, Li J, Kluger R, Yu D, Tomchick DR, Brautigam CA, Chuang DT, Structure. 2006 Feb;14(2):287-98. PMID:16472748

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