4RLA

ALTERING THE BINUCLEAR MANGANESE CLUSTER OF ARGINASE DIMINISHES THERMOSTABILITY AND CATALYTIC FUNCTION

Summary for 4RLA

• Entry DOI: 10.2210/pdb4rla/pdb
• Descriptor: ARGINASE, MANGANESE (II) ION (3 entities in total)
• Functional Keywords: hydrolase, urea cycle, arginine metabolism
• Biological source: Rattus norvegicus (Norway rat)
• Cellular location: Cytoplasm: P07824
• Total number of polymer chains: 3
• Total formula weight: 105149.97

Authors

Scolnick, L.R.,Kanyo, Z.F.,Christianson, D.W. (deposition date: 1997-05-07, release date: 1998-05-13, Last modification date: 2024-04-03)

Primary citation

Scolnick, L.R.,Kanyo, Z.F.,Cavalli, R.C.,Ash, D.E.,Christianson, D.W.
Altering the binuclear manganese cluster of arginase diminishes thermostability and catalytic function.
Biochemistry, 36:10558-10565, 1997

PubMed Abstract: Arginase is a thermostable (Tm = 75 degrees C) binuclear manganese metalloenzyme which hydrolyzes l-arginine to form l-ornithine and urea. The three-dimensional structures of native metal-depleted arginase, metal-loaded H101N arginase, and metal-depleted H101N arginase have been determined by X-ray crystallographic methods to probe the roles of the manganese ion in site A (Mn2+A) and its ligand H101 in catalysis and thermostability. We correlate these structures with thermal stability and catalytic activity measurements reported here and elsewhere [Cavalli, R. C., Burke, C. J., Kawamoto, S., Soprano, D. R., and Ash, D. E. (1994) Biochemistry 33, 10652-10657]. We conclude that the substitution of a wild-type histidine ligand to Mn2+A compromises metal binding, which in turn compromises protein thermostability and catalytic function. Therefore, a fully occupied binuclear manganese metal cluster is required for optimal catalysis and thermostability.

PubMed: 9265637
DOI: 10.1021/bi970800v

Experimental method

X-RAY DIFFRACTION (2.94 Å)