2ghm: Difference between revisions

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Revision as of 18:04, 20 March 2008

File:2ghm.gif

, resolution 2.35Å

Ligands:

Gene:

Mapk14, Crk1, Csbp1, Csbp2 (Mus musculus)

Activity:

Non-specific serine/threonine protein kinase, with EC number 2.7.11.1

Coordinates:

save as pdb, mmCIF, xml

Mutated MAP kinase P38 (Mus Musculus) in complex with Inhbitor PG-895449

OverviewOverview

A new class of tumor necrosis factor alpha (TNF-alpha) synthesis inhibitors based on an N-2,4-pyrimidine-N-phenyl-N'-phenyl urea scaffold is described. Many of these compounds showed low-nanomolar activity against lipopolysaccharide stimulated TNF-alpha production. X-ray co-crystallization studies with mutated p38alpha showed that these trisubstituted ureas interact with the ATP-binding pocket in a pseudo-bicyclic conformation brought about by the presence of an intramolecular hydrogen bonding interaction.

About this StructureAbout this Structure

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

ReferenceReference

Development of N-2,4-pyrimidine-N-phenyl-N'-phenyl ureas as inhibitors of tumor necrosis factor alpha (TNF-alpha) synthesis. Part 1., Brugel TA, Maier JA, Clark MP, Sabat M, Golebiowski A, Bookland RG, Laufersweiler MJ, Laughlin SK, Vanrens JC, De B, Hsieh LC, Mekel MJ, Janusz MJ, Bioorg Med Chem Lett. 2006 Jul 1;16(13):3510-3. Epub 2006 May 2. PMID:16632356

Page seeded by OCA on Thu Mar 20 17:04:47 2008

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

OCA

@@ Line 1: / Line 1: @@
-[[Image:2ghm.gif|left|200px]]<br /><applet load="2ghm" size="350" color="white" frame="true" align="right" spinBox="true"
+[[Image:2ghm.gif|left|200px]]
-caption="2ghm, resolution 2.35&Aring;" />
-'''Mutated MAP kinase P38 (Mus Musculus) in complex with Inhbitor PG-895449'''<br />
+ {{Structure
+|PDB= 2ghm |SIZE=350|CAPTION= <scene name='initialview01'>2ghm</scene>, resolution 2.35&Aring;
+|SITE=
+|LIGAND= <scene name='pdbligand=LIC:3-(2-CHLOROBENZYL)-1-(2-{[(1S)-2-HYDROXY-1,2-DIMETHYLPROPYL]AMINO}PYRIMIDIN-4-YL)-1-(4-METHOXYPHENYL)UREA'>LIC</scene>
+|ACTIVITY= [http://en.wikipedia.org/wiki/Non-specific_serine/threonine_protein_kinase Non-specific serine/threonine protein kinase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=2.7.11.1 2.7.11.1]
+|GENE= Mapk14, Crk1, Csbp1, Csbp2 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=10090 Mus musculus])
+}}
+'''Mutated MAP kinase P38 (Mus Musculus) in complex with Inhbitor PG-895449'''
 ==Overview==
@@ Line 7: / Line 16: @@
 ==About this Structure==
-GHM 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=LIC:'>LIC</scene> as [http://en.wikipedia.org/wiki/ligand ligand]. Active as [http://en.wikipedia.org/wiki/Non-specific_serine/threonine_protein_kinase Non-specific serine/threonine protein kinase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=2.7.11.1 2.7.11.1] Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2GHM OCA].
+GHM 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=2GHM OCA].
 ==Reference==
-Development of N-2,4-pyrimidine-N-phenyl-N'-phenyl ureas as inhibitors of tumor necrosis factor alpha (TNF-alpha) synthesis. Part 1., Brugel TA, Maier JA, Clark MP, Sabat M, Golebiowski A, Bookland RG, Laufersweiler MJ, Laughlin SK, Vanrens JC, De B, Hsieh LC, Mekel MJ, Janusz MJ, Bioorg Med Chem Lett. 2006 Jul 1;16(13):3510-3. Epub 2006 May 2. PMID:[http://ispc.weizmann.ac.il//pmbin/getpm?pmid=16632356 16632356]
+Development of N-2,4-pyrimidine-N-phenyl-N'-phenyl ureas as inhibitors of tumor necrosis factor alpha (TNF-alpha) synthesis. Part 1., Brugel TA, Maier JA, Clark MP, Sabat M, Golebiowski A, Bookland RG, Laufersweiler MJ, Laughlin SK, Vanrens JC, De B, Hsieh LC, Mekel MJ, Janusz MJ, Bioorg Med Chem Lett. 2006 Jul 1;16(13):3510-3. Epub 2006 May 2. PMID:[http://www.ncbi.nlm.nih.gov/pubmed/16632356 16632356]
 [[Category: Mus musculus]]
 [[Category: Non-specific serine/threonine protein kinase]]
@@ Line 22: / Line 31: @@
 [[Category: map kinase p38]]
-''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Feb 21 17:31:46 2008''
+''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Mar 20 17:04:47 2008''