1P8M

Structural and Functional Importance of First-Shell Metal Ligands in the Binuclear Manganese Cluster of Arginase I.

1P8M の概要

• エントリーDOI: 10.2210/pdb1p8m/pdb
• 分子名称: Arginase 1, MANGANESE (II) ION (3 entities in total)
• 機能のキーワード: hydrolase, urea cycle, binuclear manganese cluster
• 由来する生物種: Rattus norvegicus (Norway rat)
• 細胞内の位置: Cytoplasm: P07824
• タンパク質・核酸の鎖数: 3
• 化学式量合計: 102476.30

構造登録者

Cama, E.,Emig, F.A.,Ash, E.-D.,Christianson, D.W. (登録日: 2003-05-07, 公開日: 2003-06-17, 最終更新日: 2023-08-16)

主引用文献

Cama, E.,Emig, F.A.,Ash, D.E.,Christianson, D.W.
Structural and functional importance of first-shell metal ligands in the binuclear manganese cluster of arginase I.
Biochemistry, 42:7748-7758, 2003

PubMed Abstract: Arginase is a binuclear manganese metalloenzyme that hydrolyzes l-arginine to form l-ornithine and urea. The three-dimensional structures of D128E, D128N, D232A, D232C, D234E, H101N, and H101E arginases I have been determined by X-ray crystallographic methods to elucidate the roles of the first-shell metal ligands in the stability and catalytic activity of the enzyme. This work represents the first structure-based dissection of the binuclear manganese cluster using site-directed mutagenesis and X-ray crystallography. Substitution of the metal ligands compromises the catalytic activity of the enzyme, either by the loss or disruption of the metal cluster or the nucleophilic metal-bridging hydroxide ion. However, the substitution of the metal ligands or the reduction of Mn(2+)(A) or Mn(2+)(B) occupancy does not compromise enzyme-substrate affinity as reflected by K(M), which remains relatively invariant across this series of arginase variants. This implicates a nonmetal binding site for substrate l-arginine in the precatalytic Michaelis complex, as proposed based on analysis of the native enzyme structure (Kanyo, Z. F., Scolnick, L. R., Ash, D. E., and Christianson, D. W. (1996) Nature 383, 554-557).

PubMed: 12820884
DOI: 10.1021/bi030074y

実験手法

X-RAY DIFFRACTION (2.84 Å)