1uc4

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spinqualitylabelsall models 1uc4, resolution 1.80Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image

Structure of diol dehydratase complexed with (S)-1,2-propanediol

Overview

Adenosylcobalamin-dependent diol dehydratase of Klebsiella oxytoca is, apparently not stereospecific and catalyzes the conversion of both (R)-, and (S)-1,2-propanediol to propionaldehyde. To explain this unusual, property of the enzyme, we analyzed the crystal structures of diol, dehydratase in complexes with cyanocobalamin and (R)- or, (S)-1,2-propanediol. (R)- and (S)-isomers are bound in a symmetrical, manner, although the hydrogen-bonding interactions between the substrate, and the active-site residues are the same. From the position of the, adenosyl radical in the modeled "distal" conformation, it is reasonable, for the radical to abstract the pro-R and pro-S hydrogens from (R)- and, (S)-isomers, respectively. The hydroxyl groups in the substrate radicals, would migrates from C(2) to C(1) by a suprafacial shift, resulting in the, stereochemical inversion at C(1). This causes 60 degrees clockwise and 70, degrees counterclockwise rotations of the C(1)-C(2) bond of the (R)- and, (S)-isomers, respectively, if viewed from K+. A modeling study of, 1,1-gem-diol intermediates indicated that new radical center C(2) becomes, close to the methyl group of 5'-deoxyadenosine. Thus, the hydrogen, back-abstraction (recombination) from 5'-deoxyadenosine by the product, radical is structurally feasible. It was also predictable that the, substitution of the migrating hydroxyl group by a hydrogen atom from, 5'-deoxyadenosine takes place with the inversion of the configuration at, C(2) of the substrate. Stereospecific dehydration of the 1,1-gem-diol, intermediates can also be rationalized by assuming that Asp-alpha335 and, Glu-alpha170 function as base catalysts in the dehydration of the (R)- and, (S)-isomers, respectively. The structure-based mechanism and, stereochemical courses of the reaction are proposed.

About this Structure

1UC4 is a Protein complex structure of sequences from Klebsiella oxytoca with NH4, K, CNC and PGO as ligands. Active as Propanediol dehydratase, with EC number 4.2.1.28 Full crystallographic information is available from OCA.

Reference

Structural rationalization for the lack of stereospecificity in coenzyme B12-dependent diol dehydratase., Shibata N, Nakanishi Y, Fukuoka M, Yamanishi M, Yasuoka N, Toraya T, J Biol Chem. 2003 Jun 20;278(25):22717-25. Epub 2003 Apr 8. PMID:12684496

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