Binding of the unreactive substrate analog L-2-amino-3-guanidinopropionic acid (dinor-L-arginine) to human arginase I.

Edward L D'Antonio, David W Christianson

文献索引：Acta Crystallogr. Sect. F Struct. Biol. Cryst. Commun. 68(Pt 8) , 889-93, (2012)

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摘要

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 Mn(2)(2+)-HAI and Co(2)(2+)-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.