4d1p | pdb_00004d1p

Structure of human endothelial nitric oxide synthase heme domain IN COMPLEX WITH 6-((((3S, 5R)-5-(((6-AMINO-4-METHYLPYRIDIN-2-YL)METHOXY) METHYL)PYRROLIDIN-3-YL)OXY) METHYL)-4-METHYLPYRIDIN-2-AMINE

spinqualitylabelsall models 4d1p, resolution 1.73Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 4d1p is a 2 chain structure with sequence from Homo sapiens. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance. Method: X-ray diffraction, Resolution 1.731Å Ligands: ACT, BTB, GD, GOL, H4B, HEM, Q16, ZN Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT Function NOS3_HUMAN Produces nitric oxide (NO) which is implicated in vascular smooth muscle relaxation through a cGMP-mediated signal transduction pathway. NO mediates vascular endothelial growth factor (VEGF)-induced angiogenesis in coronary vessels and promotes blood clotting through the activation of platelets. Isoform eNOS13C: Lacks eNOS activity, dominant-negative form that may down-regulate eNOS activity by forming heterodimers with isoform 1. Publication Abstract from PubMed Mammals produce three isoforms of nitric oxide synthase (NOS): neuronal NOS (nNOS), inducible NOS (iNOS) and endothelial NOS (eNOS). The overproduction of NO by nNOS is associated with a number of neurodegenerative disorders; therefore, a desirable therapeutic goal is the design of drugs that target nNOS but not the other isoforms. Crystallography, coupled with computational approaches and medicinal chemistry, has played a critical role in developing highly selective nNOS inhibitors that exhibit exceptional neuroprotective properties. For historic reasons, crystallography has focused on rat nNOS and bovine eNOS because these were available in high quality; thus, their structures have been used in structure-activity-relationship studies. Although these constitutive NOSs share more than 90% sequence identity across mammalian species for each NOS isoform, inhibitor-binding studies revealed that subtle differences near the heme active site in the same NOS isoform across species still impact enzyme-inhibitor interactions. Therefore, structures of the human constitutive NOSs are indispensible. Here, the first structure of human neuronal NOS at 2.03 A resolution is reported and a different crystal form of human endothelial NOS is reported at 1.73 A resolution. Structures of human constitutive nitric oxide synthases.,Li H, Jamal J, Plaza C, Pineda SH, Chreifi G, Jing Q, Cinelli MA, Silverman RB, Poulos TL Acta Crystallogr D Biol Crystallogr. 2014 Oct 1;70(Pt 10):2667-74. doi:, 10.1107/S1399004714017064. Epub 2014 Sep 27. PMID:25286850 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See Also Nitric Oxide Synthase 3D structures

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