4E4E

Crystal Structure of the Y34F mutant of Saccharomyces cerevisiae Manganese Superoxide Dismutase

4E4E の概要

• エントリーDOI: 10.2210/pdb4e4e/pdb
• 分子名称: Superoxide dismutase [Mn], mitochondrial, MANGANESE (II) ION (3 entities in total)
• 機能のキーワード: mn superoxide dismutase, oxidoreductase
• 由来する生物種: Saccharomyces cerevisiae (Baker's yeast)
• 細胞内の位置: Mitochondrion matrix: P00447
• タンパク質・核酸の鎖数: 4
• 化学式量合計: 94318.45

構造登録者

Sheng, Y.,Cascio, D.,Valentine, J.S. (登録日: 2012-03-12, 公開日: 2012-08-22, 最終更新日: 2023-09-13)

主引用文献

Sheng, Y.,Butler Gralla, E.,Schumacher, M.,Cascio, D.,Cabelli, D.E.,Selverstone Valentine, J.
Six-coordinate manganese(3+) in catalysis by yeast manganese superoxide dismutase.
Proc.Natl.Acad.Sci.USA, 109:14314-14319, 2012

PubMed Abstract: Reduction of superoxide (O2-) by manganese-containing superoxide dismutase occurs through either a "prompt protonation" pathway, or an "inner-sphere" pathway, with the latter leading to formation of an observable Mn-peroxo complex. We recently reported that wild-type (WT) manganese superoxide dismutases (MnSODs) from Saccharomyces cerevisiae and Candida albicans are more gated toward the "prompt protonation" pathway than human and bacterial MnSODs and suggested that this could result from small structural changes in the second coordination sphere of manganese. We report here that substitution of a second-sphere residue, Tyr34, by phenylalanine (Y34F) causes the MnSOD from S. cerevisiae to react exclusively through the "inner-sphere" pathway. At neutral pH, we have a surprising observation that protonation of the Mn-peroxo complex in the mutant yeast enzyme occurs through a fast pathway, leading to a putative six-coordinate Mn(3+) species, which actively oxidizes O2- in the catalytic cycle. Upon increasing pH, the fast pathway is gradually replaced by a slow proton-transfer pathway, leading to the well-characterized five-coordinate Mn(3+). We here propose and compare two hypothetical mechanisms for the mutant yeast enzyme, differing in the structure of the Mn-peroxo complex yet both involving formation of the active six-coordinate Mn(3+) and proton transfer from a second-sphere water molecule, which has substituted for the -OH of Tyr34, to the Mn-peroxo complex. Because WT and the mutant yeast MnSOD both rest in the 2+ state and become six-coordinate when oxidized up from Mn(2+), six-coordinate Mn(3+) species could also actively function in the mechanism of WT yeast MnSODs.

PubMed: 22908245
DOI: 10.1073/pnas.1212367109

実験手法

X-RAY DIFFRACTION (1.88 Å)