3DQS
Structure of endothelial NOS heme domain in complex with a inhibitor (+-)-N1-{cis-4'-[(6"-amino-4"-methylpyridin-2"-yl)methyl]pyrrolidin-3'-yl}-N2-(4'-chlorobenzyl)ethane-1,2-diamine
Summary for 3DQS
| Entry DOI | 10.2210/pdb3dqs/pdb |
| Related | 3B3O 3DQT |
| Descriptor | Nitric oxide synthase, endothelial, CACODYLATE ION, ACETATE ION, ... (9 entities in total) |
| Functional Keywords | nitric oxide synthase heme enzyme inhibitor, blood coagulation, calmodulin-binding, cytoskeleton, fad, fmn, golgi apparatus, heme, iron, lipoprotein, membrane, metal-binding, myristate, nadp, oxidoreductase, palmitate, phosphoprotein |
| Biological source | Bos taurus (bovine) |
| Cellular location | Cell membrane: P29473 |
| Total number of polymer chains | 2 |
| Total formula weight | 96813.03 |
| Authors | Igarashi, J.,Li, H.,Poulos, T.L. (deposition date: 2008-07-09, release date: 2009-03-31, Last modification date: 2024-02-21) |
| Primary citation | Igarashi, J.,Li, H.,Jamal, J.,Ji, H.,Fang, J.,Lawton, G.R.,Silverman, R.B.,Poulos, T.L. Crystal structures of constitutive nitric oxide synthases in complex with de novo designed inhibitors. J.Med.Chem., 52:2060-2066, 2009 Cited by PubMed Abstract: New nitric oxide synthase (NOS) inhibitors were designed de novo with knowledge gathered from the studies on the nNOS-selective dipeptide inhibitors. Each of the new inhibitors consists of three fragments: an aminopyridine ring, a pyrrolidine, and a tail of various length and polarity. The in vitro inhibitory assays indicate good potency and isoform selectivity for some of the compounds. Crystal structures of these inhibitors bound to either wild type or mutant nNOS and eNOS have confirmed design expectations. The aminopyridine ring mimics the guanidinium group of L-arginine and functions as an anchor to place the compound in the NOS active site where it hydrogen bonds to a conserved Glu. The rigidity of the pyrrolidine ring places the pyrrolidine ring nitrogen between the same conserved Glu and the selective residue nNOS Asp597/eNOS Asn368, which results in similar interactions observed with the alpha-amino group of dipeptide inhibitors bound to nNOS. These structures provide additional information to help in the design of inhibitors with greater potency, physicochemical properties, and isoform selectivity. PubMed: 19296678DOI: 10.1021/jm900007a PDB entries with the same primary citation |
| Experimental method | X-RAY DIFFRACTION (2.03 Å) |
Structure validation
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