2JMU

NMR structure of the mouse thiamine triphosphatase

2JMU の概要

• エントリーDOI: 10.2210/pdb2jmu/pdb
• NMR情報: BMRB: 15063
• 分子名称: Thiamine-triphosphatase (1 entity in total)
• 機能のキーワード: thiamine triphosphatase, structural genomics, protein structure initiative, psi, center for eukaryotic structural genomics, cesg, hydrolase
• 由来する生物種: Mus musculus (house mouse)
• タンパク質・核酸の鎖数: 1
• 化学式量合計: 24243.12

構造登録者

Song, J.,Markley, J.L.,Center for Eukaryotic Structural Genomics (CESG) (登録日: 2006-12-05, 公開日: 2006-12-19, 最終更新日: 2024-05-08)

主引用文献

Song, J.,Bettendorff, L.,Tonelli, M.,Markley, J.L.
Structural basis for the catalytic mechanism of mammalian 25-kDa thiamine triphosphatase.
J.Biol.Chem., 283:10939-10948, 2008

PubMed Abstract: Mammalian soluble thiamine triphosphatase (ThTPase) is a 25-kDa cytosolic enzyme that specifically catalyzes the conversion of thiamine triphosphate (ThTP) to thiamine diphosphate and has an absolute requirement for divalent cations. We have investigated the kinetic properties of recombinant mouse thiamine triphosphatase (mThTPase) and determined its solution structure by NMR spectroscopy. Residues responsible for binding Mg(2+) and ThTP were determined from NMR titration experiments. The binding of Mg(2+) induced only a minor local conformational change, whereas ThTP binding was found to cause a more global conformational change. We derived a structural model for the mThTPase.ThTP.Mg(2+) ternary complex and concluded from this that whereas free mThTPase has an open cleft fold, the enzyme in the ternary complex adopts a tunnel fold. Our results provide a functional rationale for a number of conserved residues and suggest an essential role for Mg(2+) in catalysis. We propose a mechanism underlying the high substrate specificity of mThTPase and discuss the possible role of water molecules in enzymatic catalysis.

PubMed: 18276586
DOI: 10.1074/jbc.M709675200

実験手法

SOLUTION NMR