4cty: Difference between revisions
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<StructureSection load='4cty' size='340' side='right' caption='[[4cty]], [[Resolution|resolution]] 2.30Å' scene=''> | <StructureSection load='4cty' size='340' side='right' caption='[[4cty]], [[Resolution|resolution]] 2.30Å' scene=''> | ||
== Structural highlights == | == Structural highlights == | ||
<table><tr><td colspan='2'>[[4cty]] is a 2 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4CTY OCA]. <br> | <table><tr><td colspan='2'>[[4cty]] is a 2 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4CTY OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4CTY FirstGlance]. <br> | ||
</td></tr><tr><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=ACT:ACETATE+ION'>ACT</scene>, <scene name='pdbligand=GOL:GLYCEROL'>GOL</scene>, <scene name='pdbligand=H4B:5,6,7,8-TETRAHYDROBIOPTERIN'>H4B</scene>, <scene name='pdbligand=HEM:PROTOPORPHYRIN+IX+CONTAINING+FE'>HEM</scene>, <scene name='pdbligand=S5D:(R)-6-(2-AMINO-2-(3-(2-(6-AMINO-4-METHYLPYRIDIN-2-YL)ETHYL)PHENYL)ETHYL)-4-METHYLPYRIDIN-2-AMINE'>S5D</scene>, <scene name='pdbligand=ZN:ZINC+ION'>ZN</scene><br> | </td></tr><tr><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=ACT:ACETATE+ION'>ACT</scene>, <scene name='pdbligand=GOL:GLYCEROL'>GOL</scene>, <scene name='pdbligand=H4B:5,6,7,8-TETRAHYDROBIOPTERIN'>H4B</scene>, <scene name='pdbligand=HEM:PROTOPORPHYRIN+IX+CONTAINING+FE'>HEM</scene>, <scene name='pdbligand=S5D:(R)-6-(2-AMINO-2-(3-(2-(6-AMINO-4-METHYLPYRIDIN-2-YL)ETHYL)PHENYL)ETHYL)-4-METHYLPYRIDIN-2-AMINE'>S5D</scene>, <scene name='pdbligand=ZN:ZINC+ION'>ZN</scene><br> | ||
<tr><td class="sblockLbl"><b>[[Non-Standard_Residue|NonStd Res:]]</b></td><td class="sblockDat"><scene name='pdbligand=CAS:S-(DIMETHYLARSENIC)CYSTEINE'>CAS</scene></td></tr> | <tr><td class="sblockLbl"><b>[[Non-Standard_Residue|NonStd Res:]]</b></td><td class="sblockDat"><scene name='pdbligand=CAS:S-(DIMETHYLARSENIC)CYSTEINE'>CAS</scene></td></tr> | ||
<tr><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[4ctp|4ctp]], [[4ctq|4ctq]], [[4ctr|4ctr]], [[4ctt|4ctt]], [[4ctu|4ctu]], [[4ctv|4ctv]], [[4ctw|4ctw]], [[4ctx|4ctx]], [[4ctz|4ctz]], [[4cu0|4cu0]], [[4cu1|4cu1]]</td></tr> | <tr><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[4ctp|4ctp]], [[4ctq|4ctq]], [[4ctr|4ctr]], [[4ctt|4ctt]], [[4ctu|4ctu]], [[4ctv|4ctv]], [[4ctw|4ctw]], [[4ctx|4ctx]], [[4ctz|4ctz]], [[4cu0|4cu0]], [[4cu1|4cu1]]</td></tr> | ||
<tr><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[http://en.wikipedia.org/wiki/ | <tr><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[http://en.wikipedia.org/wiki/Nitric-oxide_synthase_(NADPH_dependent) Nitric-oxide synthase (NADPH dependent)], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=1.14.13.39 1.14.13.39] </span></td></tr> | ||
<tr><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4cty FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4cty OCA], [http://www.rcsb.org/pdb/explore.do?structureId=4cty RCSB], [http://www.ebi.ac.uk/pdbsum/4cty PDBsum]</span></td></tr> | <tr><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4cty FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4cty OCA], [http://www.rcsb.org/pdb/explore.do?structureId=4cty RCSB], [http://www.ebi.ac.uk/pdbsum/4cty PDBsum]</span></td></tr> | ||
<table> | <table> | ||
Revision as of 07:38, 4 June 2014
Structure of bovine endothelial nitric oxide synthase heme domain in complex with (R)-6-(2-Amino-2-(3-(2-(6-amino-4-methylpyridin-2-yl) ethyl)phenyl)ethyl)-4-methylpyridin-2-amineStructure of bovine endothelial nitric oxide synthase heme domain in complex with (R)-6-(2-Amino-2-(3-(2-(6-amino-4-methylpyridin-2-yl) ethyl)phenyl)ethyl)-4-methylpyridin-2-amine
Structural highlights
Publication Abstract from PubMedOverproduction of NO by nNOS is implicated in the pathogenesis of diverse neuronal disorders. Since NO signaling is involved in diverse physiological functions, selective inhibition of nNOS over other isoforms is essential to minimize side effects. A series of alpha-amino functionalized aminopyridine derivatives (3 - 8) were designed to probe the structure-activity relationship between ligand, heme propionate, and H4B. Compound 8R was identified as the most potent and selective molecule of this study, exhibiting a Ki of 24 nM for nNOS, with 273-fold and 2822-fold selectivity against iNOS and eNOS, respectively. Although crystal structures of 8R complexed with nNOS and eNOS revealed a similar binding mode, the selectivity stems from the distinct electrostatic environments in two isoforms that result in much lower inhibitor binding free energy in nNOS than in eNOS. These findings provide a basis for further development of simple, but even more selective and potent, nNOS inhibitors. Nitric Oxide Synthase Inhibitors that Interact with both a Heme Propionate and Tetrahydrobiopterin Show High Isoform Selectivity.,Kang S, Tang W, Li H, Chreifi G, Martasek P, Roman LJ, Poulos TL, Silverman RB J Med Chem. 2014 Apr 23. PMID:24758147[1] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. References
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