4cul: Difference between revisions
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==Structure of bovine endothelial nitric oxide synthase heme domain in complex with 6-acetyl-2-amino-7,7-dimethyl-7,8-dihydropteridin-4(3H)-one== | ==Structure of bovine endothelial nitric oxide synthase heme domain in complex with 6-acetyl-2-amino-7,7-dimethyl-7,8-dihydropteridin-4(3H)-one== | ||
<StructureSection load='4cul' size='340' side='right' caption='[[4cul]], [[Resolution|resolution]] 2.23Å' scene=''> | <StructureSection load='4cul' size='340' side='right'caption='[[4cul]], [[Resolution|resolution]] 2.23Å' scene=''> | ||
== Structural highlights == | == Structural highlights == | ||
<table><tr><td colspan='2'>[[4cul]] is a 2 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4CUL OCA]. For a <b>guided tour on the structure components</b> use [ | <table><tr><td colspan='2'>[[4cul]] 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=4CUL OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=4CUL 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=ARG:ARGININE'>ARG</scene>, <scene name='pdbligand=HEM:PROTOPORPHYRIN+IX+CONTAINING+FE'>HEM</scene>, <scene name='pdbligand=WSD:6-ACETYL-2-AMINO-7,7-DIMETHYL-7,8-DIHYDROPTERIDIN-4(3H)-ONE'>WSD</scene | </td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 2.23Å</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=HEM:PROTOPORPHYRIN+IX+CONTAINING+FE'>HEM</scene>, <scene name='pdbligand=WSD:6-ACETYL-2-AMINO-7,7-DIMETHYL-7,8-DIHYDROPTERIDIN-4(3H)-ONE'>WSD</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=4cul FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4cul OCA], [https://pdbe.org/4cul PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=4cul RCSB], [https://www.ebi.ac.uk/pdbsum/4cul PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=4cul ProSAT]</span></td></tr> | |||
<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[ | |||
</table> | </table> | ||
== Function == | == 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;"> | <div style="background-color:#fffaf0;"> | ||
== Publication Abstract from PubMed == | == Publication Abstract from PubMed == | ||
| Line 21: | Line 19: | ||
</div> | </div> | ||
<div class="pdbe-citations 4cul" style="background-color:#fffaf0;"></div> | <div class="pdbe-citations 4cul" style="background-color:#fffaf0;"></div> | ||
==See Also== | |||
*[[Nitric Oxide Synthase 3D structures|Nitric Oxide Synthase 3D structures]] | |||
== References == | == References == | ||
<references/> | <references/> | ||
__TOC__ | __TOC__ | ||
</StructureSection> | </StructureSection> | ||
[[Category: | [[Category: Bos taurus]] | ||
[[Category: | [[Category: Large Structures]] | ||
[[Category: | [[Category: Chreifi G]] | ||
[[Category: | [[Category: Li H]] | ||
[[Category: | [[Category: Poulos TL]] | ||
Latest revision as of 13:44, 6 November 2024
Structure of bovine endothelial nitric oxide synthase heme domain in complex with 6-acetyl-2-amino-7,7-dimethyl-7,8-dihydropteridin-4(3H)-oneStructure of bovine endothelial nitric oxide synthase heme domain in complex with 6-acetyl-2-amino-7,7-dimethyl-7,8-dihydropteridin-4(3H)-one
Structural highlights
FunctionNOS3_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 PubMedThe 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[1] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See AlsoReferences
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