Binding of the Unreactive Substrate Analog L-2-amino-3-guanidinopropionic Acid (dinor-L-arginine) to Human Arginase I
Human arginase I (HAI) is a binuclear manganese metalloenzyme that catalyzes the hydrolysis of l-arginine to form l-ornithine and urea through a metal-activated hydroxide mechanism. Since HAI regulates l-Arg bioavailability for NO biosynthesis, it is a potential drug target for the treatment of cardiovascular diseases such as atherosclerosis. X-ray crystal structures are now reported of the complexes of Mn22+-HAI and Co22+-HAI with l-2-amino-3-guanidinopropionic acid (AGPA; also known as dinor-l-arginine), an amino acid bearing a guanidinium side chain two methylene groups shorter than that of l-arginine. Hydrogen bonds to the α-carboxylate and α-amino groups of AGPA dominate enzyme–inhibitor recognition; the guanidinium group does not interact directly with the metal ions.
Published in Acta Crystallographica Section F, Volume 68, Issue 8, 2012, pages 889-893.
© Acta Crystallographica 2012, International Union of Crystallography
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