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2beu
From Proteopedia
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REACTIVITY MODULATION OF HUMAN BRANCHED-CHAIN ALPHA-KETOACID DEHYDROGENASE BY AN INTERNAL MOLECULAR SWITCH
Overview
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 ... [(full description)]
About this Structure
2BEU is a [Protein complex] structure of sequences from [Homo sapiens] with CL, K, MN, SO4, THV 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].
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
Page seeded by OCA on Tue Oct 30 16:35:13 2007
Categories: 3-methyl-2-oxobutanoate dehydrogenase (2-methylpropanoyl-transferring) | Homo sapiens | Protein complex | Brautigam, C.A. | Chuang, D.T. | Chuang, J.L. | Machius, M. | Tomchick, D.R. | Wynn, R.M. | CL | GOL | K | MN | SO4 | THV | Acylation | Branched-chain | Conformational switch | Ketoacid dehydrogenase | Maple syrup urine disease | Multi-enzyme complex | Oxidative decarboxylation | Oxidoreductase | Phosphorylation | Reactivity | Thiamine diphosphate
