1t5f

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Revision as of 00:53, 21 November 2007

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spinqualitylabelsall models 1t5f, resolution 2.20Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image

arginase I-AOH complex

Overview

Arginase is a binuclear manganese metalloenzyme that catalyzes the, hydrolysis of l-arginine to form l-ornithine and urea. Chiral L-amino, acids bearing aldehyde side chains have been synthesized in which the, electrophilic aldehyde C=O bond is isosteric with the C=N bond of, L-arginine. This substitution is intended to facilitate nucleophilic, attack by the metal-bridging hydroxide ion upon binding to the arginase, active site. Syntheses of the amino acid aldehydes have been accomplished, by reduction, oxidation, and Wittig-type reaction with a commercially, available derivative of L-glutamic acid. Amino acid aldehydes exhibit, inhibition in the micromolar range, and the X-ray crystal structure of, arginase I complexed with one of these inhibitors, (S)-2-amino-7-oxoheptanoic acid, has been determined at 2.2 A resolution., In the enzyme-inhibitor complex, the inhibitor aldehyde moiety is hydrated, to form the gem-diol: one hydroxyl group bridges the Mn(2+)(2) cluster and, donates a hydrogen bond to D128, and the second hydroxyl group donates a, hydrogen bond to E277. The binding mode of the neutral gem-diol may mimic, the binding of the neutral tetrahedral intermediate and its flanking, transition states in arginase catalysis.

About this Structure

1T5F is a Single protein structure of sequence from Rattus norvegicus with MN and DHH as ligands. Active as Arginase, with EC number 3.5.3.1 Full crystallographic information is available from OCA.

Reference

Design of amino acid aldehydes as transition-state analogue inhibitors of arginase., Shin H, Cama E, Christianson DW, J Am Chem Soc. 2004 Aug 25;126(33):10278-84. PMID:15315440

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