2hk3

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2hk3, resolution 2.300Å

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Crystal structure of mevalonate diphosphate decarboxylase from Staphylococcus aureus (orthorhombic form)

Overview

Mevalonate diphosphate decarboxylase (MDD) catalyzes the ATP-dependent, decarboxylation of mevalonate 5-diphosphate (MDP) to form isopentenyl, pyrophosphate, a ubiquitous precursor for isoprenoid biosynthesis. MDD is, a poorly understood component of this important metabolic pathway., Complementation of a temperature-sensitive yeast mutant by the putative, mdd genes of Trypanosoma brucei and Staphylococcus aureus provides, proof-of-function. Crystal structures of MDD from T. brucei (TbMDD, at 1.8, A resolution) and S. aureus (SaMDD, in two distinct crystal forms, each, diffracting to 2.3 A resolution) have been determined. Gel-filtration, chromatography and analytical ultracentrifugation experiments indicate, that TbMDD is predominantly monomeric in solution while SaMDD is dimeric., The new crystal structures and comparison with that of the yeast, Saccharomyces cerevisiae enzyme (ScMDD) reveal the structural basis for, this variance in quaternary structure. The presence of an ordered sulfate, in the structure of TbMDD reveals for the first time details of a ligand, binding in the MDD active site and, in conjunction with well-ordered water, molecules, comparisons with the related enzyme mevalonate kinase, structural and biochemical data derived on ScMDD and SaMDD, allows us to, model a ternary complex with MDP and ATP. This model facilitates, discussion of the molecular determinants of substrate recognition and, contributions made by specific residues to the enzyme mechanism.

About this Structure

2HK3 is a Single protein structure of sequence from Staphylococcus aureus. Active as Diphosphomevalonate decarboxylase, with EC number 4.1.1.33 Full crystallographic information is available from OCA.

Reference

Crystal Structures of Trypanosoma brucei and Staphylococcus aureus Mevalonate Diphosphate Decarboxylase Inform on the Determinants of Specificity and Reactivity., Byres E, Alphey MS, Smith TK, Hunter WN, J Mol Biol. 2007 Aug 10;371(2):540-53. Epub 2007 Jun 4. PMID:17583736

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