1ZSP

Contribution to Structure and Catalysis of Tyrosine 34 in Human Manganese Superoxide Dismutase

1ZSP の概要

• エントリーDOI: 10.2210/pdb1zsp/pdb
• 関連するPDBエントリー: 1ZUQ 1zte
• 分子名称: Superoxide dismutase [Mn], mitochondrial, MANGANESE (II) ION (3 entities in total)
• 機能のキーワード: mnsod, manganese superoxide dismutase, y34a mutation, oxidoreductase
• 由来する生物種: Homo sapiens (human)
• 細胞内の位置: Mitochondrion matrix: P04179
• タンパク質・核酸の鎖数: 2
• 化学式量合計: 44391.91

構造登録者

Hearn, A.S.,Perry, J.J.,Cabelli, D.E.,Tainer, J.A.,Nick, H.S.,Silverman, D.S. (登録日: 2005-05-24, 公開日: 2006-05-02, 最終更新日: 2023-08-23)

主引用文献

Perry, J.J.,Hearn, A.S.,Cabelli, D.E.,Nick, H.S.,Tainer, J.A.,Silverman, D.N.
Contribution of human manganese superoxide dismutase tyrosine 34 to structure and catalysis.
Biochemistry, 48:3417-3424, 2009

PubMed Abstract: Superoxide dismutase (SOD) enzymes are critical in controlling levels of reactive oxygen species (ROS) that are linked to aging, cancer, and neurodegenerative disease. Superoxide (O(2)(*-)) produced during respiration is removed by the product of the SOD2 gene, the homotetrameric manganese superoxide dismutase (MnSOD). Here, we examine the structural and catalytic roles of the highly conserved active-site residue Tyr34, based upon structure-function studies of MnSOD enzymes with mutations at this site. Substitution of Tyr34 with five different amino acids retained the active-site protein structure and assembly but caused a substantial decrease in the catalytic rate constant for the reduction of superoxide. The rate constant for formation of the product inhibition complex also decreases but to a much lesser extent, resulting in a net increase in the level of product inhibited form of the mutant enzymes. Comparisons of crystal structures and catalytic rates also suggest that one mutation, Y34V, interrupts the hydrogen-bonded network, which is associated with a rapid dissociation of the product-inhibited complex. Notably, with three of the Tyr34 mutants, we also observe an intermediate in catalysis, which has not been reported previously. Thus, these mutants establish a means of trapping a catalytic intermediate that promises to help elucidate the mechanism of catalysis.

PubMed: 19265433
DOI: 10.1021/bi8023288

実験手法

X-RAY DIFFRACTION (1.9 Å)