1PT9

Crystal Structure Analysis of the DIII Component of Transhydrogenase with a Thio-Nicotinamide Nucleotide Analogue

1PT9 の概要

• エントリーDOI: 10.2210/pdb1pt9/pdb
• 関連するPDBエントリー: 1PTJ
• 分子名称: NAD(P) transhydrogenase, mitochondrial, SULFATE ION, 7-THIONICOTINAMIDE-ADENINE-DINUCLEOTIDE PHOSPHATE, ... (5 entities in total)
• 機能のキーワード: transhydrogenase, thio-nicotinamide, mitochondria, proton translocation, oxidoreductase
• 由来する生物種: Homo sapiens (human)
• 細胞内の位置: Mitochondrion inner membrane ; Multi-pass membrane protein ; Matrix side : Q13423
• タンパク質・核酸の鎖数: 2
• 化学式量合計: 46458.56

構造登録者

Singh, A.,Venning, J.D.,Quirk, P.G.,van Boxel, G.I.,Rodrigues, D.J.,White, S.A.,Jackson, J.B. (登録日: 2003-06-23, 公開日: 2003-10-07, 最終更新日: 2023-08-16)

主引用文献

Singh, A.,Venning, J.D.,Quirk, P.G.,Van Boxel, G.I.,Rodrigues, D.J.,White, S.A.,Jackson, J.B.
Interactions between transhydrogenase and thio-nicotinamide analogues of NAD(H) and NADP(H) underline the importance of nucleotide conformational changes in coupling to proton translocation
J.Biol.Chem., 278:33208-33216, 2003

PubMed Abstract: Transhydrogenase couples the reduction of NADP+ by NADH to inward proton translocation across mitochondrial and bacterial membranes. The coupling reactions occur within the protein by long distance conformational changes. In intact transhydrogenase and in complexes formed from the isolated, nucleotide-binding components, thio-NADP(H) is a good analogue for NADP(H), but thio-NAD(H) is a poor analogue for NAD(H). Crystal structures of the nucleotide-binding components show that the twists of the 3-carbothiamide groups of thio-NADP+ and of thio-NAD+ (relative to the planes of the pyridine rings), which are defined by the dihedral, Xam, are altered relative to the twists of the 3-carboxamide groups of the physiological nucleotides. The finding that thio-NADP+ is a good substrate despite an increased Xam value shows that approach of the NADH prior to hydride transfer is not obstructed by the S atom in the analogue. That thio-NAD(H) is a poor substrate appears to be the result of failure in the conformational change that establishes the ground state for hydride transfer. This might be a consequence of restricted rotation of the 3-carbothiamide group during the conformational change.

PubMed: 12791694
DOI: 10.1074/jbc.M303061200

実験手法

X-RAY DIFFRACTION (2.42 Å)