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4IE2

Crystal structure of human Arginase-2 complexed with inhibitor 1h

Summary for 4IE2
Entry DOI10.2210/pdb4ie2/pdb
Related1D3V 1PQ3
DescriptorArginase-2, mitochondrial, MANGANESE (II) ION, BENZAMIDINE, ... (6 entities in total)
Functional Keywordsmetalloenzyme, alpha/beta fold, hydrolase, arginine metabolism, manganese, mitochondrion, hydrolase-hydrolase inhibitor complex, hydrolase/hydrolase inhibitor
Biological sourceHomo sapiens (human)
Cellular locationMitochondrion : P78540
Total number of polymer chains3
Total formula weight101604.08
Authors
Primary citationGolebiowski, 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: 23453840
DOI: 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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