1T5F
arginase I-AOH complex
Summary for 1T5F
| Entry DOI | 10.2210/pdb1t5f/pdb |
| Descriptor | Arginase 1, MANGANESE (II) ION, (S)-2-AMINO-7,7-DIHYDROXYHEPTANOIC ACID, ... (4 entities in total) |
| Functional Keywords | arginase, aoh, hydrolase |
| Biological source | Rattus norvegicus (Norway rat) |
| Cellular location | Cytoplasm: P07824 |
| Total number of polymer chains | 3 |
| Total formula weight | 102401.07 |
| Authors | Shin, H.,Cama, E.,Christianson, D.W. (deposition date: 2004-05-04, release date: 2005-05-17, Last modification date: 2024-02-14) |
| Primary citation | Shin, H.,Cama, E.,Christianson, D.W. Design of amino acid aldehydes as transition-state analogue inhibitors of arginase J.Am.Chem.Soc., 126:10278-10284, 2004 Cited by PubMed Abstract: 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. PubMed: 15315440DOI: 10.1021/ja047788w PDB entries with the same primary citation |
| Experimental method | X-RAY DIFFRACTION (2.2 Å) |
Structure validation
Download full validation report
