4CA2

ENGINEERING THE HYDROPHOBIC POCKET OF CARBONIC ANHYDRASE II

4CA2 の概要

• エントリーDOI: 10.2210/pdb4ca2/pdb
• 分子名称: CARBONIC ANHYDRASE II, ZINC ION, MERCURY (II) ION, ... (4 entities in total)
• 機能のキーワード: lyase(oxo-acid)
• 由来する生物種: Homo sapiens (human)
• 細胞内の位置: Cytoplasm : P00918
• タンパク質・核酸の鎖数: 1
• 化学式量合計: 29555.06

構造登録者

Alexander, R.S.,Christianson, D.W. (登録日: 1991-06-08, 公開日: 1992-10-31, 最終更新日: 2024-02-28)

主引用文献

Alexander, R.S.,Nair, S.K.,Christianson, D.W.
Engineering the hydrophobic pocket of carbonic anhydrase II.
Biochemistry, 30:11064-11072, 1991

PubMed Abstract: Wild-type and mutant human carbonic anhydrases II, where mutations have been made in the hydrophobic pocket of the active site, have been studied by X-ray crystallographic methods. Specifically, mutations at Val-143 (the base of the pocket) lead to significant changes in catalytic activity and protein structure. The obliteration of a well-defined pocket in the Val-143----Phe and Val-143----Tyr mutants results in significantly diminished enzyme activity [(5 x 10(4))-fold and (3 x 10(5))-fold, respectively]; however, the activity of the Val-143----His mutant is diminished less (10(2)-fold), and deepening the pocket in the Val-143----Gly mutant results in only a 2-fold decrease in activity [Fierke et al., 1991 (preceding paper in this issue)]. These results indicate that the hydrophobic pocket is important for substrate association with the enzyme, but there are probably several catalytically acceptable substrate trajectories through this region of the enzyme structure. Additionally, each mutant protein exhibits long-range (ca. 10-15 A) compensatory structural changes which accommodate the Val-143 substitution. As such, the genetic-structural approach represented in this work serves as a three-dimensional paradigm for the redesign of specificity pockets in other protein catalysts.

PubMed: 1932029
DOI: 10.1021/bi00110a008

実験手法

X-RAY DIFFRACTION (2.1 Å)