2bfb: Difference between revisions

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[[Image:2bfb.gif|left|200px]]
{{Seed}}
[[Image:2bfb.png|left|200px]]


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{{STRUCTURE_2bfb|  PDB=2bfb  |  SCENE=  }}  
{{STRUCTURE_2bfb|  PDB=2bfb  |  SCENE=  }}  


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




==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.
The line below this paragraph, {{ABSTRACT_PUBMED_16472748}}, adds the Publication Abstract to the page
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{{ABSTRACT_PUBMED_16472748}}


==About this Structure==
==About this Structure==
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[[Category: Conformational switch,reactivity]]
[[Category: Conformational switch,reactivity]]
[[Category: Oxidoreductase,ketoacid dehydrogenase,branched-chain,multi-enzyme complex,acylation,oxidative decarboxylation,maple syrup urine disease,thiamine diphosphate,phosphorylation]]
[[Category: Oxidoreductase,ketoacid dehydrogenase,branched-chain,multi-enzyme complex,acylation,oxidative decarboxylation,maple syrup urine disease,thiamine diphosphate,phosphorylation]]
''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Sat May  3 20:12:49 2008''
 
''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Tue Jul 29 05:27:42 2008''
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