2HKE

Mevalonate diphosphate decarboxylase from Trypanosoma brucei

2HKE の概要

• エントリーDOI: 10.2210/pdb2hke/pdb
• 関連するPDBエントリー: 2HK2 2HK3
• 分子名称: Diphosphomevalonate decarboxylase, putative, SULFATE ION (3 entities in total)
• 機能のキーワード: mevalonate diphosphate decarboxylase, diphosphomevalonate decarboxylase, decarboxylase, lyase
• 由来する生物種: Trypanosoma brucei
• タンパク質・核酸の鎖数: 2
• 化学式量合計: 84466.89

構造登録者

Byres, E.,Alphey, M.S.,Hunter, W.N. (登録日: 2006-07-04, 公開日: 2007-06-12, 最終更新日: 2023-10-25)

主引用文献

Byres, E.,Alphey, M.S.,Smith, T.K.,Hunter, W.N.
Crystal Structures of Trypanosoma brucei and Staphylococcus aureus Mevalonate Diphosphate Decarboxylase Inform on the Determinants of Specificity and Reactivity
J.Mol.Biol., 371:540-553, 2007

PubMed 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.

PubMed: 17583736
DOI: 10.1016/j.jmb.2007.05.094

実験手法

X-RAY DIFFRACTION (1.8 Å)