3nld: Difference between revisions

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~~{{Seed}}~~

~~[[Image:3nld.jpg|left|200px]]~~

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==Structure of endothelial nitric oxide synthase heme domain complexed with 6-{{(3'S,4'S)-3'-[2"-(3'''-fluorophenethylamino)ethoxy]pyrrolidin-4'-yl}methyl}-4-methylpyridin-2-amine==

~~The line below this paragraph~~, ~~containing~~ "~~STRUCTURE_3nld~~"~~, creates the~~ "~~Structure Box~~" ~~on the page~~.

~~You may change the PDB parameter~~ (~~which sets the PDB file loaded into the applet~~)

== Structural highlights ==

~~or the SCENE parameter~~ (which ~~sets the initial scene displayed when the page~~ is ~~loaded~~),

<table><tr><td colspan='2'>[[3nld]] is a 2 chain structure with sequence from [https://en.wikipedia.org/wiki/Bos_taurus Bos taurus]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3NLD OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=3NLD FirstGlance]. <br>

~~or leave~~ the ~~SCENE parameter empty for the default display~~.

</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 2.285Å</td></tr>

-->

<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><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=JSS:6-{[(3S,4S)-4-(2-{[2-(3-FLUOROPHENYL)ETHYL]AMINO}ETHOXY)PYRROLIDIN-3-YL]METHYL}-4-METHYLPYRIDIN-2-AMINE'>JSS</scene>, <scene name='pdbligand=ZN:ZINC+ION'>ZN</scene></td></tr>

~~{{STRUCTURE_3nld| PDB~~=~~3nld | SCENE~~= }}

<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=3nld FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3nld OCA], [https://pdbe.org/3nld PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=3nld RCSB], [https://www.ebi.ac.uk/pdbsum/3nld PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=3nld ProSAT]</span></td></tr>

</table>

== Function ==

[https://www.uniprot.org/uniprot/NOS3_BOVIN NOS3_BOVIN] 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.

== 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~~ of ~~endothelial nitric oxide synthase heme domain complexed with 6~~-~~{{(3'S~~,~~4'S)-3'-[2"-(3'''-fluorophenethylamino)ethoxy]pyrrolidin-4'-yl}methyl}-4-methylpyridin-2-amine===~~

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>

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br>

</div>

~~<!--~~

==See Also==

~~The line below this paragraph, {{ABSTRACT_PUBMED_20958055}}, adds the Publication Abstract to the page~~

*[[Nitric Oxide Synthase 3D structures|Nitric Oxide Synthase 3D structures]]

~~(as it appears on PubMed at http://www.pubmed.gov), where 20958055 is the PubMed ID number.~~

== References ==

~~-->~~

~~{{ABSTRACT_PUBMED_20958055}}~~

__TOC__

</StructureSection>

==~~About this Structure~~==

~~3NLD is a 2 chains structure with sequences 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=3NLD OCA~~].

==~~Reference~~==

<~~ref group="xtra">PMID:20958055<~~/~~ref~~><~~references group="xtra"~~/>

[[Category: Bos taurus]]

[[Category: ~~Nitric-oxide synthase~~]]

[[Category: Large Structures]]

[[Category: Delker~~, S L.~~]]

[[Category: Delker SL]]

[[Category: Ji, H.]]

[[Category: Ji H]]

[[Category: Li, H.]]

[[Category: Li H]]

[[Category: Martasek, P.]]

[[Category: Martasek P]]

[[Category: Poulos~~, T L.~~]]

[[Category: Poulos TL]]

[[Category: Roman, L.]]

[[Category: Roman L]]

[[Category: Silverman~~, R B.]]~~

[[Category: Silverman RB]]

~~[[Category: Heme enzyme~~]]

~~[[Category: Nitric oxide synthase]]~~

~~[[Category: Oxidoreductase]]~~

~~[[Category: Substrate inhibitor]]~~

~~''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Wed Nov 3 11:10:47 2010''~~

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@@ Line 1: / Line 1: @@
-{{Seed}}
-[[Image:3nld.jpg|left|200px]]
-<!--
+==Structure of endothelial nitric oxide synthase heme domain complexed with 6-{{(3'S,4'S)-3'-[2"-(3'''-fluorophenethylamino)ethoxy]pyrrolidin-4'-yl}methyl}-4-methylpyridin-2-amine==
-The line below this paragraph, containing "STRUCTURE_3nld", creates the "Structure Box" on the page.
+<StructureSection load='3nld' size='340' side='right'caption='[[3nld]], [[Resolution|resolution]] 2.29&Aring;' scene=''>
-You may change the PDB parameter (which sets the PDB file loaded into the applet)
+== Structural highlights ==
-or the SCENE parameter (which sets the initial scene displayed when the page is loaded),
+<table><tr><td colspan='2'>[[3nld]] is a 2 chain structure with sequence from [https://en.wikipedia.org/wiki/Bos_taurus Bos taurus]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3NLD OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=3NLD FirstGlance]. <br>
-or leave the SCENE parameter empty for the default display.
+</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 2.285&#8491;</td></tr>
--->
+<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><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=JSS:6-{[(3S,4S)-4-(2-{[2-(3-FLUOROPHENYL)ETHYL]AMINO}ETHOXY)PYRROLIDIN-3-YL]METHYL}-4-METHYLPYRIDIN-2-AMINE'>JSS</scene>, <scene name='pdbligand=ZN:ZINC+ION'>ZN</scene></td></tr>
-{{STRUCTURE_3nld|  PDB=3nld  |  SCENE=  }}
+<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=3nld FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3nld OCA], [https://pdbe.org/3nld PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=3nld RCSB], [https://www.ebi.ac.uk/pdbsum/3nld PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=3nld ProSAT]</span></td></tr>
+</table>
+== Function ==
+[https://www.uniprot.org/uniprot/NOS3_BOVIN NOS3_BOVIN] 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.
+<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 of endothelial nitric oxide synthase heme domain complexed with 6-{{(3'S,4'S)-3'-[2"-(3'''-fluorophenethylamino)ethoxy]pyrrolidin-4'-yl}methyl}-4-methylpyridin-2-amine===
+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>
+From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
+</div>
+<div class="pdbe-citations 3nld" style="background-color:#fffaf0;"></div>
-<!--
+==See Also==
-The line below this paragraph, {{ABSTRACT_PUBMED_20958055}}, adds the Publication Abstract to the page
+*[[Nitric Oxide Synthase 3D structures|Nitric Oxide Synthase 3D structures]]
-(as it appears on PubMed at http://www.pubmed.gov), where 20958055 is the PubMed ID number.
+== References ==
--->
+<references/>
-{{ABSTRACT_PUBMED_20958055}}
+__TOC__
+</StructureSection>
-==About this Structure==
-NLD is a 2 chains structure with sequences 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=3NLD OCA].
-==Reference==
-<ref group="xtra">PMID:20958055</ref><references group="xtra"/>
 [[Category: Bos taurus]]
-[[Category: Nitric-oxide synthase]]
+[[Category: Large Structures]]
-[[Category: Delker, S L.]]
+[[Category: Delker SL]]
-[[Category: Ji, H.]]
+[[Category: Ji H]]
-[[Category: Li, H.]]
+[[Category: Li H]]
-[[Category: Martasek, P.]]
+[[Category: Martasek P]]
-[[Category: Poulos, T L.]]
+[[Category: Poulos TL]]
-[[Category: Roman, L.]]
+[[Category: Roman L]]
-[[Category: Silverman, R B.]]
+[[Category: Silverman RB]]
-[[Category: Heme enzyme]]
-[[Category: Nitric oxide synthase]]
-[[Category: Oxidoreductase]]
-[[Category: Substrate inhibitor]]
-''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Wed Nov  3 11:10:47 2010''