1P8P

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

Summary for 1P8P

• Entry DOI: 10.2210/pdb1p8p/pdb
• Related: 3RLA
• Descriptor: Arginase 1, MANGANESE (II) ION (3 entities in total)
• Functional Keywords: hydrolase, urea cycle, arginine metabolism, binuclear manganese cluster
• Biological source: Rattus norvegicus (Norway rat)
• Cellular location: Cytoplasm: P07824
• Total number of polymer chains: 3
• Total formula weight: 102362.09

Authors

Cama, E.,Emig, F.A.,Ash, D.E.,Christianson, D.W. (deposition date: 2003-05-07, release date: 2003-06-17, Last modification date: 2023-08-16)

Primary citation

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

Experimental method

X-RAY DIFFRACTION (2.5 Å)