3nlj: Difference between revisions
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==Structure of neuronal nitric oxide synthase D597N/M336V/Y706A triple mutant heme domain complexed with 6-{{(3'R,4'R)-3'-[2"-(3'''-fluorophenethylamino)ethoxy] pyrrolidin-4'-yl}methyl}-4-methylpyridin-2-amine== | ==Structure of neuronal nitric oxide synthase D597N/M336V/Y706A triple mutant heme domain complexed with 6-{{(3'R,4'R)-3'-[2"-(3'''-fluorophenethylamino)ethoxy] pyrrolidin-4'-yl}methyl}-4-methylpyridin-2-amine== | ||
<StructureSection load='3nlj' size='340' side='right' caption='[[3nlj]], [[Resolution|resolution]] 2.20Å' scene=''> | <StructureSection load='3nlj' size='340' side='right' caption='[[3nlj]], [[Resolution|resolution]] 2.20Å' scene=''> | ||
== Structural highlights == | == Structural highlights == | ||
<table><tr><td colspan='2'>[[3nlj]] is a 2 chain structure with sequence from [http://en.wikipedia.org/wiki/ | <table><tr><td colspan='2'>[[3nlj]] is a 2 chain structure with sequence from [http://en.wikipedia.org/wiki/Buffalo_rat Buffalo rat]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3NLJ OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=3NLJ FirstGlance]. <br> | ||
</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=ACT:ACETATE+ION'>ACT</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=JRR:6-{[(3R,4R)-4-(2-{[2-(3-FLUOROPHENYL)ETHYL]AMINO}ETHOXY)PYRROLIDIN-3-YL]METHYL}-4-METHYLPYRIDIN-2-AMINE'>JRR</scene></td></tr> | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=ACT:ACETATE+ION'>ACT</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=JRR:6-{[(3R,4R)-4-(2-{[2-(3-FLUOROPHENYL)ETHYL]AMINO}ETHOXY)PYRROLIDIN-3-YL]METHYL}-4-METHYLPYRIDIN-2-AMINE'>JRR</scene></td></tr> | ||
<tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[3nld|3nld]], [[3nle|3nle]], [[3nlf|3nlf]], [[3nlg|3nlg]], [[3nlh|3nlh]], [[3nli|3nli]], [[3nlk|3nlk]], [[3nlm|3nlm]], [[3nln|3nln]], [[3nlo|3nlo]], [[3nlp|3nlp]], [[3nlq|3nlq]], [[3nlr|3nlr]], [[3nlt|3nlt]], [[3nlu|3nlu]], [[3nlv|3nlv]], [[3nlw|3nlw]], [[3nlx|3nlx]], [[3nly|3nly]], [[3nlz|3nlz]], [[3nm0|3nm0]]</td></tr> | <tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[3nld|3nld]], [[3nle|3nle]], [[3nlf|3nlf]], [[3nlg|3nlg]], [[3nlh|3nlh]], [[3nli|3nli]], [[3nlk|3nlk]], [[3nlm|3nlm]], [[3nln|3nln]], [[3nlo|3nlo]], [[3nlp|3nlp]], [[3nlq|3nlq]], [[3nlr|3nlr]], [[3nlt|3nlt]], [[3nlu|3nlu]], [[3nlv|3nlv]], [[3nlw|3nlw]], [[3nlx|3nlx]], [[3nly|3nly]], [[3nlz|3nlz]], [[3nm0|3nm0]]</td></tr> | ||
<tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">Nos1, Bnos ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=10116 | <tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">Nos1, Bnos ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=10116 Buffalo rat])</td></tr> | ||
<tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[http://en.wikipedia.org/wiki/Nitric- | <tr id='activity'><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 id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=3nlj FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3nlj OCA], [http://www.rcsb.org/pdb/explore.do?structureId=3nlj RCSB], [http://www.ebi.ac.uk/pdbsum/3nlj PDBsum]</span></td></tr> | <tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=3nlj FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3nlj OCA], [http://pdbe.org/3nlj PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=3nlj RCSB], [http://www.ebi.ac.uk/pdbsum/3nlj PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=3nlj ProSAT]</span></td></tr> | ||
</table> | </table> | ||
== Function == | == Function == | ||
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From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | ||
</div> | </div> | ||
<div class="pdbe-citations 3nlj" style="background-color:#fffaf0;"></div> | |||
==See Also== | ==See Also== | ||
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__TOC__ | __TOC__ | ||
</StructureSection> | </StructureSection> | ||
[[Category: | [[Category: Buffalo rat]] | ||
[[Category: Delker, S L]] | [[Category: Delker, S L]] | ||
[[Category: Li, H]] | [[Category: Li, H]] | ||
Revision as of 21:29, 4 August 2016
Structure of neuronal nitric oxide synthase D597N/M336V/Y706A triple mutant heme domain complexed with 6-{{(3'R,4'R)-3'-[2"-(3-fluorophenethylamino)ethoxy] pyrrolidin-4'-yl}methyl}-4-methylpyridin-2-amine
Structural highlights
Function[NOS1_RAT] Produces nitric oxide (NO) which is a messenger molecule with diverse functions throughout the body. In the brain and peripheral nervous system, NO displays many properties of a neurotransmitter. Inhibitory transmitter for non-adrenergic and non-cholinergic nerves in the colorectum. Probably has nitrosylase activity and mediates cysteine S-nitrosylation of cytoplasmic target proteins such SRR. Inhibitory transmitter for non-adrenergic and non-cholinergic nerves in the colorectum. Publication Abstract from PubMedNeuronal nitric oxide synthase (nNOS) represents an important therapeutic target for the prevention of brain injury and the treatment of various neurodegenerative disorders. A series of trans-substituted amino pyrrolidinomethyl 2-aminopyridine derivatives (8-34) was designed and synthesized. A structure-activity relationship analysis led to the discovery of low nanomolar nNOS inhibitors ((+/-)-32 and (+/-)-34) with more than 1000-fold selectivity for nNOS over eNOS. Four enantiomerically pure isomers of 3'-[2-(3-fluorophenethylamino)ethoxy]pyrrolidin-4'-yl}methyl}-4-methy lpyridin-2-amine (4) also were synthesized. It was found that (3'R,4'R)-4 can induce enzyme elasticity to generate a new "hot spot" for ligand binding. The inhibitor adopts a unique binding mode, the same as that observed for (3'R,4'R)-3'-[2-(3-fluorophenethylamino)ethylamino]pyrrolidin-4'-yl}m ethyl}-4-methylpyridin-2-amine ((3'R,4'R)-3) ( J. Am. Chem. Soc. 2010 , 132 ( 15 ), 5437 - 5442 ). On the basis of structure-activity relationships of 8-34 and different binding conformations of the cis and trans isomers of 3 and 4, critical structural requirements of the NOS active site for ligand binding are revealed. Exploration of the Active Site of Neuronal Nitric Oxide Synthase by the Design and Synthesis of Pyrrolidinomethyl 2-Aminopyridine Derivatives.,Ji H, Delker SL, Li H, Martasek P, Roman LJ, Poulos TL, Silverman RB J Med Chem. 2010 Oct 19. PMID:20958055[1] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See AlsoReferences
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