1dm6: Difference between revisions
New page: left|200px<br /><applet load="1dm6" size="450" color="white" frame="true" align="right" spinBox="true" caption="1dm6, resolution 1.95Å" /> '''BOVINE ENDOTHELIAL N... |
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[[Image:1dm6.jpg|left|200px]]<br /><applet load="1dm6" size=" | [[Image:1dm6.jpg|left|200px]]<br /><applet load="1dm6" size="350" color="white" frame="true" align="right" spinBox="true" | ||
caption="1dm6, resolution 1.95Å" /> | caption="1dm6, resolution 1.95Å" /> | ||
'''BOVINE ENDOTHELIAL NITRIC OXIDE SYNTHASE HEME DOMAIN COMPLEXED WITH N-(4-CHLOROPHENYL)-N'-HYDROXYGUANIDINE (H4B FREE)'''<br /> | '''BOVINE ENDOTHELIAL NITRIC OXIDE SYNTHASE HEME DOMAIN COMPLEXED WITH N-(4-CHLOROPHENYL)-N'-HYDROXYGUANIDINE (H4B FREE)'''<br /> | ||
==Overview== | ==Overview== | ||
Nitric oxide is generated under normal and pathophysiological conditions | Nitric oxide is generated under normal and pathophysiological conditions by three distinct isoforms of nitric oxide synthase (NOS). A small-molecule inhibitor of NOS (3-Br-7-nitroindazole, 7-NIBr) is profoundly neuroprotective in mouse models of stroke and Parkinson's disease. We report the crystal structure of the catalytic heme domain of endothelial NOS complexed with 7-NIBr at 1.65 A resolution. Critical to the binding of 7-NIBr at the substrate site is the adoption by eNOS of an altered conformation, in which a key glutamate residue swings out toward one of the heme propionate groups. Perturbation of the heme propionate ensues and eliminates the cofactor tetrahydrobiopterin-heme interaction. We also present three crystal structures that reveal how alterations at the substrate site facilitate 7-NIBr and structurally dissimilar ligands to occupy the cofactor site. | ||
==About this Structure== | ==About this Structure== | ||
1DM6 is a [http://en.wikipedia.org/wiki/Single_protein Single protein] structure of sequence from [http://en.wikipedia.org/wiki/Bos_taurus Bos taurus] with ACT, CAC, ZN, HEM and PH3 as [http://en.wikipedia.org/wiki/ligands ligands]. Active as [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] Full crystallographic information is available from [http:// | 1DM6 is a [http://en.wikipedia.org/wiki/Single_protein Single protein] structure of sequence from [http://en.wikipedia.org/wiki/Bos_taurus Bos taurus] with <scene name='pdbligand=ACT:'>ACT</scene>, <scene name='pdbligand=CAC:'>CAC</scene>, <scene name='pdbligand=ZN:'>ZN</scene>, <scene name='pdbligand=HEM:'>HEM</scene> and <scene name='pdbligand=PH3:'>PH3</scene> as [http://en.wikipedia.org/wiki/ligands ligands]. Active as [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] Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1DM6 OCA]. | ||
==Reference== | ==Reference== | ||
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[[Category: Li, H.]] | [[Category: Li, H.]] | ||
[[Category: Martasek, P.]] | [[Category: Martasek, P.]] | ||
[[Category: Masters, B | [[Category: Masters, B S.S.]] | ||
[[Category: Poulos, T | [[Category: Poulos, T L.]] | ||
[[Category: Raman, C | [[Category: Raman, C S.]] | ||
[[Category: Southan, G | [[Category: Southan, G J.]] | ||
[[Category: ACT]] | [[Category: ACT]] | ||
[[Category: CAC]] | [[Category: CAC]] | ||
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[[Category: alpha-beta fold]] | [[Category: alpha-beta fold]] | ||
''Page seeded by [http:// | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Feb 21 12:18:05 2008'' | ||
Revision as of 10:18, 21 February 2008
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BOVINE ENDOTHELIAL NITRIC OXIDE SYNTHASE HEME DOMAIN COMPLEXED WITH N-(4-CHLOROPHENYL)-N'-HYDROXYGUANIDINE (H4B FREE)
Overview
Nitric oxide is generated under normal and pathophysiological conditions by three distinct isoforms of nitric oxide synthase (NOS). A small-molecule inhibitor of NOS (3-Br-7-nitroindazole, 7-NIBr) is profoundly neuroprotective in mouse models of stroke and Parkinson's disease. We report the crystal structure of the catalytic heme domain of endothelial NOS complexed with 7-NIBr at 1.65 A resolution. Critical to the binding of 7-NIBr at the substrate site is the adoption by eNOS of an altered conformation, in which a key glutamate residue swings out toward one of the heme propionate groups. Perturbation of the heme propionate ensues and eliminates the cofactor tetrahydrobiopterin-heme interaction. We also present three crystal structures that reveal how alterations at the substrate site facilitate 7-NIBr and structurally dissimilar ligands to occupy the cofactor site.
About this Structure
1DM6 is a Single protein structure of sequence from Bos taurus with ACT, CAC, ZN, HEM and PH3 as ligands. Active as Nitric-oxide synthase, with EC number 1.14.13.39 Full crystallographic information is available from OCA.
Reference
Crystal structure of nitric oxide synthase bound to nitro indazole reveals a novel inactivation mechanism., Raman CS, Li H, Martasek P, Southan G, Masters BS, Poulos TL, Biochemistry. 2001 Nov 13;40(45):13448-55. PMID:11695891
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