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Crystal Structure of the Mn2+2-Human Arginase I-AGPA ComplexCrystal Structure of the Mn2+2-Human Arginase I-AGPA Complex
Structural highlights
Disease[ARGI1_HUMAN] Defects in ARG1 are the cause of argininemia (ARGIN) [MIM:207800]; also known as hyperargininemia. Argininemia is a rare autosomal recessive disorder of the urea cycle. Arginine is elevated in the blood and cerebrospinal fluid, and periodic hyperammonemia occurs. Clinical manifestations include developmental delay, seizures, mental retardation, hypotonia, ataxia, progressive spastic quadriplegia.[1] [2] Publication Abstract from PubMedHuman 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 alpha-carboxylate and alpha-amino groups of AGPA dominate enzyme-inhibitor recognition; the guanidinium group does not interact directly with the metal ions. Binding of the unreactive substrate analog L-2-amino-3-guanidinopropionic acid (dinor-L-arginine) to human arginase I.,D'Antonio EL, Christianson DW Acta Crystallogr Sect F Struct Biol Cryst Commun. 2012 Aug;68(Pt 8):889-93. Epub , 2012 Jul 27. PMID:22869115[3] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See AlsoReferences
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