3nlg: Difference between revisions

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-[[Image:3nlg.png|left|200px]]
+==Structure of endothelial nitric oxide synthase heme domain complexed with 6-{{(3'S,4'R)-3'-[2"-(3'''-fluorophenethylamino)ethoxy]pyrrolidin-4'-yl}methyl}-4-methylpyridin-2-amine==
+<StructureSection load='3nlg' size='340' side='right' caption='[[3nlg]], [[Resolution|resolution]] 2.38&Aring;' scene=''>
+== Structural highlights ==
+<table><tr><td colspan='2'>[[3nlg]] is a 2 chain structure with sequence from [http://en.wikipedia.org/wiki/Bos_taurus Bos taurus]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3NLG OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=3NLG 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=CAD:CACODYLIC+ACID'>CAD</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=JSR:6-{[(3R,4S)-4-(2-{[2-(3-FLUOROPHENYL)ETHYL]AMINO}ETHOXY)PYRROLIDIN-3-YL]METHYL}-4-METHYLPYRIDIN-2-AMINE'>JSR</scene>, <scene name='pdbligand=ZN:ZINC+ION'>ZN</scene></td></tr>
+<tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[3nld|3nld]], [[3nle|3nle]], [[3nlf|3nlf]], [[3nlh|3nlh]], [[3nli|3nli]], [[3nlj|3nlj]], [[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">NOS3 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9913 Bos taurus])</td></tr>
+<tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[http://en.wikipedia.org/wiki/Nitric-oxide_synthase Nitric-oxide synthase], 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=3nlg FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3nlg OCA], [http://www.rcsb.org/pdb/explore.do?structureId=3nlg RCSB], [http://www.ebi.ac.uk/pdbsum/3nlg PDBsum]</span></td></tr>
+</table>
+<div style="background-color:#fffaf0;">
+== Publication Abstract from PubMed ==
+Neuronal 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.
-{{STRUCTURE_3nlg|  PDB=3nlg  |  SCENE=  }}
+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<ref>PMID:20958055</ref>
-===Structure of endothelial nitric oxide synthase heme domain complexed with 6-{{(3'S,4'R)-3'-[2"-(3'''-fluorophenethylamino)ethoxy]pyrrolidin-4'-yl}methyl}-4-methylpyridin-2-amine===
+From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
+</div>
-{{ABSTRACT_PUBMED_20958055}}
-==About this Structure==
-[[3nlg]] is a 2 chain structure with sequence from [http://en.wikipedia.org/wiki/Bos_taurus Bos taurus]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3NLG OCA].
 ==See Also==
 *[[Nitric Oxide Synthase|Nitric Oxide Synthase]]
+== References ==
-==Reference==
+<references/>
-<ref group="xtra">PMID:020958055</ref><references group="xtra"/>
+__TOC__
+</StructureSection>
 [[Category: Bos taurus]]
 [[Category: Nitric-oxide synthase]]
-[[Category: Delker, S L.]]
+[[Category: Delker, S L]]
-[[Category: Ji, H.]]
+[[Category: Ji, H]]
-[[Category: Li, H.]]
+[[Category: Li, H]]
-[[Category: Martasek, P.]]
+[[Category: Martasek, P]]
-[[Category: Poulos, T L.]]
+[[Category: Poulos, T L]]
-[[Category: Roman, L.]]
+[[Category: Roman, L]]
-[[Category: Silverman, R B.]]
+[[Category: Silverman, R B]]
 [[Category: Heme enzyme]]
 [[Category: Nitric oxide synthase]]
 [[Category: Oxidoreductase]]
 [[Category: Substrate inhibitor]]