2bfc

File:2bfc.gif

spinqualitylabelsall models 2bfc, resolution 1.64Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image

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

OverviewOverview

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.

About this StructureAbout this Structure

2BFC is a Protein complex structure of sequences from Homo sapiens with K, MN, TZD and GOL as ligands. Active as 3-methyl-2-oxobutanoate dehydrogenase (2-methylpropanoyl-transferring), with EC number 1.2.4.4 Structure known Active Site: AC1. Full crystallographic information is available from OCA.

ReferenceReference

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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