| Structural highlights
4ie2 is a 3 chain structure with sequence from Human. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
| | Ligands: | , , , |
| Related: | 1d3v, 1pq3 |
| Gene: | ARG2 (HUMAN) |
| Activity: | Arginase, with EC number 3.5.3.1 |
| Resources: | FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT |
Function
[ARGI2_HUMAN] May play a role in the regulation of extra-urea cycle arginine metabolism and also in down-regulation of nitric oxide synthesis. Extrahepatic arginase functions to regulate L-arginine bioavailability to NO synthase. Since NO synthase is found in the penile corpus cavernosum smooth muscle, the clitoral corpus cavernosum and the vagina, arginase II plays a role in both male and female sexual arousal. It is therefore a potential target for the treatment of male and female sexual arousal disorders.
Publication Abstract from PubMed
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.
2-Substituted-2-amino-6-boronohexanoic acids as arginase inhibitors.,Golebiowski A, Paul Beckett R, Van Zandt M, Ji MK, Whitehouse D, Ryder TR, Jagdmann E, Andreoli M, Mazur A, Padmanilayam M, Cousido-Siah A, Mitschler A, Ruiz FX, Podjarny A, Schroeter H Bioorg Med Chem Lett. 2013 Apr 1;23(7):2027-30. doi: 10.1016/j.bmcl.2013.02.024. , Epub 2013 Feb 13. PMID:23453840[1]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
References
- ↑ Golebiowski A, Paul Beckett R, Van Zandt M, Ji MK, Whitehouse D, Ryder TR, Jagdmann E, Andreoli M, Mazur A, Padmanilayam M, Cousido-Siah A, Mitschler A, Ruiz FX, Podjarny A, Schroeter H. 2-Substituted-2-amino-6-boronohexanoic acids as arginase inhibitors. Bioorg Med Chem Lett. 2013 Apr 1;23(7):2027-30. doi: 10.1016/j.bmcl.2013.02.024. , Epub 2013 Feb 13. PMID:23453840 doi:http://dx.doi.org/10.1016/j.bmcl.2013.02.024
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