1PL4

Crystal Structure of human MnSOD Y166F mutant

1PL4 の概要

• エントリーDOI: 10.2210/pdb1pl4/pdb
• 分子名称: Superoxide dismutase [Mn], mitochondrial, MANGANESE (II) ION (3 entities in total)
• 機能のキーワード: 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: 4
• 化学式量合計: 89088.20

構造登録者

Fan, L.,Tainer, J.A. (登録日: 2003-06-06, 公開日: 2003-12-16, 最終更新日: 2023-08-16)

主引用文献

Hearn, A.S.,Fan, L.,Lepock, J.R.,Luba, J.P.,Greenleaf, W.B.,Cabelli, D.E.,Tainer, J.A.,Nick, H.S.,Silverman, D.N.
Amino acid substitution at the dimeric interface of human manganese superoxide dismutase
J.Biol.Chem., 279:5861-5866, 2004

PubMed Abstract: The side chains of His30 and Tyr166 from adjacent subunits in the homotetramer human manganese superoxide dismutase (Mn-SOD) form a hydrogen bond across the dimer interface and participate in a hydrogen-bonded network that extends to the active site. Compared with wild-type Mn-SOD, the site-specific mutants H30N, Y166F, and the corresponding double mutant showed 10-fold decreases in steady-state constants for catalysis measured by pulse radiolysis. The observation of no additional effect upon the second mutation is an example of cooperatively interacting residues. A similar effect was observed in the thermal stability of these enzymes; the double mutant did not reduce the major unfolding transition to an extent greater than either single mutant. The crystal structures of these site-specific mutants each have unique conformational changes, but each has lost the hydrogen bond across the dimer interface, which results in a decrease in catalysis. These same mutations caused an enhancement of the dissociation of the product-inhibited complex. That is, His30 and Tyr166 in wild-type Mn-SOD act to prolong the lifetime of the inhibited complex. This would have a selective advantage in blocking a cellular overproduction of toxic H2O2.

PubMed: 14638684
DOI: 10.1074/jbc.M311310200

実験手法

X-RAY DIFFRACTION (1.47 Å)