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

作者：D'Antonio Edward L; Christianson David W^*

来源：Acta Crystallographica Section F-Structural Biology and Crystallization Communications, 2012, 68: 889-893.

DOI：10.1107/S1744309112027820

• human arginase I
• l-2-amino-3-guanidinopropionic acid
• dinor-l-arginine

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 a-carboxylate and a-amino groups of AGPA dominate enzymeinhibitor recognition; the guanidinium group does not interact directly with the metal ions.

• 出版日期2012-8