title: Binding of the unreactive substrate analog L-2-amino-3-guanidinopropionic acid (dinor-L-arginine) to human arginase I.
abstract: 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.
authors.affiliation: Roy and Diana Vagelos Laboratories, Department of Chemistry, University of Pennsylvania, Philadelphia, PA 19104-6323, USA.
authors.forename: Edward L
authors.initials: EL
authors.lastname: D'Antonio
authors.forename: David W
authors.initials: DW
authors.lastname: Christianson
mesh_terms: D000409:Alanine / Q000031:analogs & derivatives* / Q000737:chemistry / Q000378:metabolism; D001119:Arginase / Q000737:chemistry* / Q000378:metabolism; D055162:Biocatalysis; D006801:Humans; D008958:Models, Molecular; D011485:Protein Binding; D054730:Protein Interaction Domains and Motifs; D013379:Substrate Specificity
chemical_list: C023997:alpha-amino-beta-guanidinopropionic acid; C574619:ARG1 protein, human; D001119:Arginase; D000409:Alanine