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Structure of a unique binuclear manganese cluster in arginase

Nature volume 383, pages 554–557 (1996)Cite this article

Abstract

EACH individual excretes roughly 10 kg of urea per year, as a result of the hydrolysis of arginine in the final cytosolic step of the urea cycle1. This reaction allows the disposal of nitrogenous waste from protein catabolism, and is catalysed by the liver arginase enzyme2. In other tissues that lack a complete urea cycle, arginase regulates cellular arginine and ornithine concentrations for biosynthetic reactions3, including nitric oxide synthesis: in the macrophage, arginase activity is reciprocally coordinated with that of NO synthase to modulate NO-dependent cytotoxicity4–9. The bioinorganic chemistry of arginase is particularly rich because this enzyme is one of very few that specifically requires a spin-coupled Mn2+ –Mn2+ cluster for catalytic activity in vitro and in vivo10. The 2.1 Å-resolution crystal structure of trimeric11 rat liver arginase reveals that this unique metal cluster resides at the bottom of an active-site cleft that is 15 Å deep. Analysis of the structure indicates that arginine hydrolysis is achieved by a metal-activated solvent molecule which symmetrically bridges the two Mn2+ ions.

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Authors and Affiliations

  1. Department of Chemistry, University of Pennsylvania, 231S. 34th Street, Philadelphia, Pennsylvania, 19104-6323, USA

    Zoltan F. Kanyo, Laura R. Scolnick & David W. Christianson

  2. Department of Biochemistry, Temple University School of Medicine, Philadelphia, Pennsylvania, 19140, USA

    David E. Ash

Authors
  1. Zoltan F. Kanyo
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  2. Laura R. Scolnick
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  3. David E. Ash
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  4. David W. Christianson
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Kanyo, Z., Scolnick, L., Ash, D. et al. Structure of a unique binuclear manganese cluster in arginase. Nature 383, 554–557 (1996). https://doi.org/10.1038/383554a0

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