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4k5j

From Proteopedia

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Current revision

Structure of bovine endothelial nitric oxide synthase heme domain in complex with (S)-1,3-bis((2-amino-4-methylpyridin-6-yl)-methoxy)-butan-4-amine

Structural highlights

4k5j is a 2 chain structure with sequence from Bos taurus. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Method:	X-ray diffraction, Resolution 2.36Å
Ligands:	, , , , , ,
Resources:	FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Function

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

To develop potent and selective nNOS inhibitors, new double-headed molecules with chiral linkers that derive from natural amino acids or their derivatives have been designed. The new structures contain two ether bonds, which greatly simplifies the synthesis and accelerates structure optimization. Inhibitor (R)-6b exhibits a potency of 32nM against nNOS and is 475 and 244 more selective for nNOS over eNOS and iNOS, respectively. Crystal structures show that the additional binding between the aminomethyl moiety of 6b and the two heme propionates in nNOS, but not eNOS, is the structural basis for its high selectivity. This work demonstrates the importance of stereochemistry in this class of molecules, which significantly influences the potency and selectivity of the inhibitors. The structure-activity information gathered here provides a guide for future structure optimization.

Chiral linkers to improve selectivity of double-headed neuronal nitric oxide synthase inhibitors.,Jing Q, Li H, Chreifi G, Roman LJ, Martasek P, Poulos TL, Silverman RB Bioorg Med Chem Lett. 2013 Oct 15;23(20):5674-9. doi: 10.1016/j.bmcl.2013.08.034., Epub 2013 Aug 14. PMID:23993333^[1]

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

References

↑ Jing Q, Li H, Chreifi G, Roman LJ, Martasek P, Poulos TL, Silverman RB. Chiral linkers to improve selectivity of double-headed neuronal nitric oxide synthase inhibitors. Bioorg Med Chem Lett. 2013 Oct 15;23(20):5674-9. doi: 10.1016/j.bmcl.2013.08.034., Epub 2013 Aug 14. PMID:23993333 doi:10.1016/j.bmcl.2013.08.034

1 Structural highlights
2 Function
3 Publication Abstract from PubMed
4 See Also
5 References

Proteopedia Page Contributors and Editors (what is this?)

OCA

Retrieved from "http://52.214.119.220/wiki/index.php/4k5j"

Categories: Bos taurus | Large Structures | Li H | Poulos TL

@@ Line 4: / Line 4: @@
 == Structural highlights ==
 <table><tr><td colspan='2'>[[4k5j]] 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=4K5J OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=4K5J FirstGlance]. <br>
-</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=CAS:S-(DIMETHYLARSENIC)CYSTEINE'>CAS</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=Q14:6-[({(2S)-1-AMINO-4-[(6-AMINO-4-METHYLPYRIDIN-2-YL)METHOXY]BUTAN-2-YL}OXY)METHYL]-4-METHYLPYRIDIN-2-AMINE'>Q14</scene>, <scene name='pdbligand=ZN:ZINC+ION'>ZN</scene></td></tr>
+</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 2.36&#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=CAS:S-(DIMETHYLARSENIC)CYSTEINE'>CAS</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=Q14:6-[({(2S)-1-AMINO-4-[(6-AMINO-4-METHYLPYRIDIN-2-YL)METHOXY]BUTAN-2-YL}OXY)METHYL]-4-METHYLPYRIDIN-2-AMINE'>Q14</scene>, <scene name='pdbligand=ZN:ZINC+ION'>ZN</scene></td></tr>
 <tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=4k5j FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4k5j OCA], [https://pdbe.org/4k5j PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=4k5j RCSB], [https://www.ebi.ac.uk/pdbsum/4k5j PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=4k5j ProSAT]</span></td></tr>
 </table>

4k5j

From Proteopedia

Current revision

Structure of bovine endothelial nitric oxide synthase heme domain in complex with (S)-1,3-bis((2-amino-4-methylpyridin-6-yl)-methoxy)-butan-4-amine

Structural highlights

Function

Publication Abstract from PubMed

See Also

References

Contents

Proteopedia Page Contributors and Editors (what is this?)

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