1foj: Difference between revisions

Revision as of 16:34, 2 May 2008

BOVINE ENDOTHELIAL NITRIC OXIDE SYNTHASE HEME DOMAIN COMPLEXED WITH 7-NITROINDAZOLE-2-CARBOXAMIDINE (H4B PRESENT)

OverviewOverview

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 StructureAbout this Structure

1FOJ is a Single protein structure of sequence from Bos taurus. Full crystallographic information is available from OCA.

ReferenceReference

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 Page seeded by OCA on Fri May 2 16:34:41 2008

Proteopedia Page Contributors and Editors (what is this?)Proteopedia Page Contributors and Editors (what is this?)

OCA

@@ Line 1: / Line 1: @@
 [[Image:1foj.gif|left|200px]]
- {{Structure
+<!--
-|PDB= 1foj |SIZE=350|CAPTION= <scene name='initialview01'>1foj</scene>, resolution 2.10&Aring;
+The line below this paragraph, containing "STRUCTURE_1foj", creates the "Structure Box" on the page.
-|SITE=
+You may change the PDB parameter (which sets the PDB file loaded into the applet)
-|LIGAND= <scene name='pdbligand=7I2:7-NITROINDAZOLE-2-CARBOXAMIDINE'>7I2</scene>, <scene name='pdbligand=7NI:7-NITROINDAZOLE'>7NI</scene>, <scene name='pdbligand=ACT:ACETATE+ION'>ACT</scene>, <scene name='pdbligand=CAC:CACODYLATE+ION'>CAC</scene>, <scene name='pdbligand=HEM:PROTOPORPHYRIN+IX+CONTAINING+FE'>HEM</scene>, <scene name='pdbligand=ZN:ZINC+ION'>ZN</scene>
+or the SCENE parameter (which sets the initial scene displayed when the page is loaded),
-|ACTIVITY= <span class='plainlinks'>[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] </span>
+or leave the SCENE parameter empty for the default display.
-|GENE=
+-->
-|DOMAIN=
+{{STRUCTURE_1foj|  PDB=1foj  |  SCENE=  }}
-|RELATEDENTRY=
-|RESOURCES=<span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=1foj FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1foj OCA], [http://www.ebi.ac.uk/pdbsum/1foj PDBsum], [http://www.rcsb.org/pdb/explore.do?structureId=1foj RCSB]</span>
-}}
 '''BOVINE ENDOTHELIAL NITRIC OXIDE SYNTHASE HEME DOMAIN COMPLEXED WITH 7-NITROINDAZOLE-2-CARBOXAMIDINE (H4B PRESENT)'''
@@ Line 31: / Line 28: @@
 [[Category: Poulos, T L.]]
 [[Category: Raman, C S.]]
-[[Category: alpha-beta fold]]
+[[Category: Alpha-beta fold]]
-[[Category: nitric oxide synthase]]
+[[Category: Nitric oxide synthase]]
+''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Fri May  2 16:34:41 2008''
-''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Sun Mar 30 20:27:06 2008''