View source for 4cvg


==Structure of bovine endothelial nitric oxide synthase heme domain (H4B-free) supplemented with 50uM Zn acetate and with poor binding of 6-acetyl-2-amino-7,7-dimethyl-7,8-dihydropteridin-4(3H)-one.==
<StructureSection load='4cvg' size='340' side='right'caption='[[4cvg]], [[Resolution|resolution]] 2.31&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[4cvg]] 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=4CVG OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=4CVG FirstGlance]. <br>
</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 2.31&#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=ARG:ARGININE'>ARG</scene>, <scene name='pdbligand=CAS:S-(DIMETHYLARSENIC)CYSTEINE'>CAS</scene>, <scene name='pdbligand=GOL:GLYCEROL'>GOL</scene>, <scene name='pdbligand=HEM:PROTOPORPHYRIN+IX+CONTAINING+FE'>HEM</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=4cvg FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4cvg OCA], [https://pdbe.org/4cvg PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=4cvg RCSB], [https://www.ebi.ac.uk/pdbsum/4cvg PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=4cvg 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.
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== Publication Abstract from PubMed ==
The nitric oxide synthase (NOS) dimer is stabilized by a Zn2+ ion coordinated to four symmetry related Cys residues exactly along the dimer 2-fold axis. Each of the two essential tetrahydrobiopterin (H4B) molecules in the dimer interacts directly with the heme, and each H4B molecule is about 15 A from the Zn2+. We have solved the crystal structures of the bovine endothelial NOS (eNOS) dimer oxygenase domain bound to three different pterin analogs which reveal an intimate structural communication between the H4B and Zn2+ sites. The binding of one of these compounds, 6-Acetyl-2-amino-7,7-dimethyl-7,8-dihydro-4(3H)-pteridinone, 1, to the pterin site and Zn2+ binding are mutually exclusive. Compound 1 both directly and indirectly disrupts hydrogen bonding between key residues in the Zn2+ binding motif, resulting in destabilization of the dimer and a complete disruption of the Zn2+ site. Addition of excess Zn2+ stabilizes the Zn2+ site at the expense of weakened binding of 1. The unique structural features of 1 that disrupt the dimer interface are extra methyl groups that extend into the dimer interface and force a slight opening of the dimer thus resulting in disruption of the Zn2+ site. These results illustrate a very delicate balance of forces and structure at the dimer interface which must be maintained to properly form the Zn2+, pterin, and substrate binding sites.

Communication Between the Zinc and Tetrahydrobiopterin Binding Sites in Nitric Oxide Synthase.,Chreifi G, Li H, McInnes CR, Gibson CL, Suckling CJ, Poulos TL Biochemistry. 2014 May 12. PMID:24819538<ref>PMID:24819538</ref>

From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
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<div class="pdbe-citations 4cvg" style="background-color:#fffaf0;"></div>

==See Also==
*[[Nitric Oxide Synthase 3D structures|Nitric Oxide Synthase 3D structures]]
== References ==
<references/>
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</StructureSection>
[[Category: Bos taurus]]
[[Category: Large Structures]]
[[Category: Chreifi G]]
[[Category: Li H]]
[[Category: Poulos TL]]