2orr: Difference between revisions

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Revision as of 19:03, 20 March 2008

File:2orr.gif

, resolution 2.00Å

Ligands:

, and

Gene:

Nos2, Inosl (Mus musculus)

Activity:

Nitric-oxide synthase, with EC number 1.14.13.39

Coordinates:

save as pdb, mmCIF, xml

Murine Inducible Nitric Oxide Synthase Oxygenase Domain (Delta 114) 4-(Benzo[1,3]dioxol-5-yloxy)-2-(4-imidazol-1-yl-phenoxy)-pyrimidine Complex

OverviewOverview

By the screening of a combinatorial library for inhibitors of nitric oxide (NO) formation by the inducible isoform of nitric oxide synthase (iNOS) using a whole-cell assay, 2-(imidazol-1-yl)pyrimidines were identified. Compounds were found to inhibit the dimerization of iNOS monomers, thus preventing the formation of the dimeric, active form of the enzyme. Optimization led to the selection of the potent, selective, and orally available iNOS dimerization inhibitor, 21b, which significantly ameliorated adjuvant-induced arthritis in a rat model. Analysis of the crystal structure of the 21b--iNOS monomer complex provided a rationalization for both the SAR and the mechanism by which 21b blocks the formation of the protein--protein interaction present in the dimeric form of iNOS.

About this StructureAbout this Structure

2ORR is a Single protein structure of sequence from Mus musculus. Full crystallographic information is available from OCA.

ReferenceReference

Design, synthesis, and activity of 2-imidazol-1-ylpyrimidine derived inducible nitric oxide synthase dimerization inhibitors., Davey DD, Adler M, Arnaiz D, Eagen K, Erickson S, Guilford W, Kenrick M, Morrissey MM, Ohlmeyer M, Pan G, Paradkar VM, Parkinson J, Polokoff M, Saionz K, Santos C, Subramanyam B, Vergona R, Wei RG, Whitlow M, Ye B, Zhao ZS, Devlin JJ, Phillips G, J Med Chem. 2007 Mar 22;50(6):1146-57. Epub 2007 Feb 23. PMID:17315988

Page seeded by OCA on Thu Mar 20 18:03:37 2008

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

OCA

@@ Line 1: / Line 1: @@
-[[Image:2orr.gif|left|200px]]<br /><applet load="2orr" size="350" color="white" frame="true" align="right" spinBox="true"
+[[Image:2orr.gif|left|200px]]
-caption="2orr, resolution 2.00&Aring;" />
-'''Murine Inducible Nitric Oxide Synthase Oxygenase Domain (Delta 114) 4-(Benzo[1,3]dioxol-5-yloxy)-2-(4-imidazol-1-yl-phenoxy)-pyrimidine Complex'''<br />
+ {{Structure
+|PDB= 2orr |SIZE=350|CAPTION= <scene name='initialview01'>2orr</scene>, resolution 2.00&Aring;
+|SITE=
+|LIGAND= <scene name='pdbligand=HEM:PROTOPORPHYRIN+IX+CONTAINING+FE'>HEM</scene>, <scene name='pdbligand=333:4-(1,3-BENZODIOXOL-5-YLOXY)-2-[4-(1H-IMIDAZOL-1-YL)PHENOXY]PYRIMIDINE'>333</scene> and <scene name='pdbligand=EDO:1,2-ETHANEDIOL'>EDO</scene>
+|ACTIVITY= [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]
+|GENE= Nos2, Inosl ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=10090 Mus musculus])
+}}
+'''Murine Inducible Nitric Oxide Synthase Oxygenase Domain (Delta 114) 4-(Benzo[1,3]dioxol-5-yloxy)-2-(4-imidazol-1-yl-phenoxy)-pyrimidine Complex'''
 ==Overview==
@@ Line 7: / Line 16: @@
 ==About this Structure==
-ORR is a [http://en.wikipedia.org/wiki/Single_protein Single protein] structure of sequence from [http://en.wikipedia.org/wiki/Mus_musculus Mus musculus] with <scene name='pdbligand=HEM:'>HEM</scene>, <scene name='pdbligand=333:'>333</scene> and <scene name='pdbligand=EDO:'>EDO</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=2ORR OCA].
+ORR is a [[Single protein]] structure of sequence from [http://en.wikipedia.org/wiki/Mus_musculus Mus musculus]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2ORR OCA].
 ==Reference==
-Design, synthesis, and activity of 2-imidazol-1-ylpyrimidine derived inducible nitric oxide synthase dimerization inhibitors., Davey DD, Adler M, Arnaiz D, Eagen K, Erickson S, Guilford W, Kenrick M, Morrissey MM, Ohlmeyer M, Pan G, Paradkar VM, Parkinson J, Polokoff M, Saionz K, Santos C, Subramanyam B, Vergona R, Wei RG, Whitlow M, Ye B, Zhao ZS, Devlin JJ, Phillips G, J Med Chem. 2007 Mar 22;50(6):1146-57. Epub 2007 Feb 23. PMID:[http://ispc.weizmann.ac.il//pmbin/getpm?pmid=17315988 17315988]
+Design, synthesis, and activity of 2-imidazol-1-ylpyrimidine derived inducible nitric oxide synthase dimerization inhibitors., Davey DD, Adler M, Arnaiz D, Eagen K, Erickson S, Guilford W, Kenrick M, Morrissey MM, Ohlmeyer M, Pan G, Paradkar VM, Parkinson J, Polokoff M, Saionz K, Santos C, Subramanyam B, Vergona R, Wei RG, Whitlow M, Ye B, Zhao ZS, Devlin JJ, Phillips G, J Med Chem. 2007 Mar 22;50(6):1146-57. Epub 2007 Feb 23. PMID:[http://www.ncbi.nlm.nih.gov/pubmed/17315988 17315988]
 [[Category: Mus musculus]]
 [[Category: Nitric-oxide synthase]]
@@ Line 24: / Line 33: @@
 [[Category: l-arginine monooxygenase]]
 [[Category: nitric oxide]]
-[[Category: nos]]
+[[Category: no]]
-''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Feb 21 18:21:49 2008''
+''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Mar 20 18:03:37 2008''