4IE2
Crystal structure of human Arginase-2 complexed with inhibitor 1h
Summary for 4IE2
Entry DOI | 10.2210/pdb4ie2/pdb |
Related | 1D3V 1PQ3 |
Descriptor | Arginase-2, mitochondrial, MANGANESE (II) ION, BENZAMIDINE, ... (6 entities in total) |
Functional Keywords | metalloenzyme, alpha/beta fold, hydrolase, arginine metabolism, manganese, mitochondrion, hydrolase-hydrolase inhibitor complex, hydrolase/hydrolase inhibitor |
Biological source | Homo sapiens (human) |
Cellular location | Mitochondrion : P78540 |
Total number of polymer chains | 3 |
Total formula weight | 101604.08 |
Authors | Cousido-Siah, A.,Mitschler, A.,Ruiz, F.X.,Beckett, P.,Van Zandt, M.C.,Ji, M.K.,Whitehouse, D.,Ryder, T.,Jagdmann, E.,Andreoli, M.,Mazur, A.,Padmanilayam, M.,Schroeter, H.,Golebiowski, A.,Podjarny, A. (deposition date: 2012-12-13, release date: 2013-03-20, Last modification date: 2023-09-20) |
Primary citation | Golebiowski, A.,Paul Beckett, R.,Van Zandt, M.,Ji, M.K.,Whitehouse, D.,Ryder, T.R.,Jagdmann, E.,Andreoli, M.,Mazur, A.,Padmanilayam, M.,Cousido-Siah, A.,Mitschler, A.,Ruiz, F.X.,Podjarny, A.,Schroeter, H. 2-Substituted-2-amino-6-boronohexanoic acids as arginase inhibitors. Bioorg.Med.Chem.Lett., 23:2027-2030, 2013 Cited by PubMed Abstract: Substitution at the alpha center of the known human arginase inhibitor 2-amino-6-boronohexanoic acid (ABH) is acceptable in the active site pockets of both human arginase I and arginase II. In particular, substituents with a tertiary amine linked via a two carbon chain show improved inhibitory potency for both enzyme isoforms. This potency improvement can be rationalized by X-ray crystallography, which shows a water-mediated contact between the basic nitrogen and the carboxylic acid side chain of Asp200, which is situated at the mouth of the active site pocket of arginase II (Asp181 in arginase I). We believe that this is the first literature report of compounds with improved arginase inhibitory activity, relative to ABH, and represents a promising starting point for further optimization of in vitro potency and the identification of better tool molecules for in vivo investigations of the potential pathophysiological roles of arginases. PubMed: 23453840DOI: 10.1016/j.bmcl.2013.02.024 PDB entries with the same primary citation |
Experimental method | X-RAY DIFFRACTION (2.2082 Å) |
Structure validation
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