D'Antonio Edward L, Christianson David W
Roy and Diana Vagelos Laboratories, Department of Chemistry, University of Pennsylvania, Philadelphia, PA 19104-6323, USA.
Acta Crystallogr Sect F Struct Biol Cryst Commun. 2012 Aug 1;68(Pt 8):889-93. doi: 10.1107/S1744309112027820. Epub 2012 Jul 27.
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.
人精氨酸酶I（HAI）是一种双核锰金属酶，通过金属激活的氢氧化物机制催化L-精氨酸水解形成L-鸟氨酸和尿素。由于HAI调节用于一氧化氮生物合成的L-精氨酸的生物利用度，它是治疗动脉粥样硬化等心血管疾病的潜在药物靶点。现在报道了Mn(2)(2+)-HAI和Co(2)(2+)-HAI与L-2-氨基-3-胍基丙酸（AGPA；也称为二去甲-L-精氨酸）形成的复合物的X射线晶体结构，AGPA是一种侧链胍基比L-精氨酸短两个亚甲基的氨基酸。与AGPA的α-羧基和α-氨基形成的氢键主导了酶-抑制剂识别；胍基不直接与金属离子相互作用。
