Crystal Structures of Trypanosoma Brucei and Staphylococcus Aureus Mevalonate Diphosphate Decarboxylase Inform on the Determinants of Specificity and Reactivity.
From: Division of Biological Chemistry and Molecular Microbiology, College of Life Sciences, University of Dundee, Dundee DD1 5EH, UK.
Journal of molecular biology
- Publish Date: Aug 2007
- ISSN: 0022-2836
- Volume: 371
- Issue: 2
- Pages: 540-53
- Medium: Print
- Language: English
- Citation (JAMA): Byres Emma, Alphey Magnus S, Smith Terry K, et al. Crystal Structures of Trypanosoma Brucei and Staphylococcus Aureus Mevalonate Diphosphate Decarboxylase Inform on the Determinants of Specificity and Reactivity.. J. Mol. Biol. Aug 2007;371:540-53
Abstract
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.
Mesh Headings (Keywords): Adenosine Triphosphate, Amino Acid Sequence, Animals, Binding Sites, Carboxy-Lyases, Conserved Sequence, Crystallography, X-Ray, Mevalonic Acid, Models, Molecular, Molecular Sequence Data, Protein Structure, Tertiary, Sequence Alignment, Staphylococcus aureus, Structural Homology, Protein, Substrate Specificity, Trypanosoma brucei brucei
Check for Full Text / PubMed Unique Identifier (PMID): 17583736
This abstract is part of PubMed, a service of the U.S. National Library of Medicine. PubMed includes more than 17 million citations from MEDLINE and other life science journals for biomedical articles. See Copyright and Disclaimers.
Linked medical terms appearing on this page are added by Healia to help readers find more information and are not part of the original PubMed document.
The data herein was last updated on July 8th, 2008 and may not reflect the most current and accurate data available from NLM.