2hg2
From Proteopedia
|
Structure of Lactaldehyde Dehydrogenase
Overview
Aldehyde dehydrogenases catalyze the oxidation of aldehyde substrates to, the corresponding carboxylic acids. Lactaldehyde dehydrogenase from, Escherichia coli (aldA gene product, P25553) is an NAD(+)-dependent enzyme, implicated in the metabolism of l-fucose and l-rhamnose. During the, heterologous expression and purification of taxadiene synthase from the, Pacific yew, lactaldehyde dehydrogenase from E. coli was identified as a, minor (</=5%) side-product subsequent to its unexpected crystallization., Accordingly, we now report the serendipitous crystal structure, determination of unliganded lactaldehyde dehydrogenase from E. coli, determined by the technique of multiple isomorphous replacement using, anomalous scattering at 2.2 A resolution. Additionally, we report the, crystal structure of the ternary enzyme complex with products lactate and, NADH at 2.1 A resolution, and the crystal structure of the enzyme complex, with NADPH at 2.7 A resolution. The structure of the ternary complex, reveals that the nicotinamide ring of the cofactor is disordered between, two conformations: one with the ring positioned in the active site in the, so-called hydrolysis conformation, and another with the ring extended out, of the active site into the solvent region, designated the out, conformation. This represents the first crystal structure of an aldehyde, dehydrogenase-product complex. The active site pocket in which lactate, binds is more constricted than that of medium-chain dehydrogenases such as, the YdcW gene product of E. coli. The structure of the binary complex with, NADPH reveals the first view of the structural basis of specificity for, NADH: the negatively charged carboxylate group of E179 destabilizes the, binding of the 2'-phosphate group of NADPH sterically and, electrostatically, thereby accounting for the lack of enzyme activity with, this cofactor.
About this Structure
2HG2 is a Single protein structure of sequence from Escherichia coli with as ligand. Full crystallographic information is available from OCA.
Reference
Crystal structure of lactaldehyde dehydrogenase from Escherichia coli and inferences regarding substrate and cofactor specificity., Di Costanzo L, Gomez GA, Christianson DW, J Mol Biol. 2007 Feb 16;366(2):481-93. Epub 2006 Nov 10. PMID:17173928
Page seeded by OCA on Wed Jan 23 15:20:33 2008
