2jbp: Difference between revisions

Revision as of 12:12, 23 January 2008

PROTEIN KINASE MK2 IN COMPLEX WITH AN INHIBITOR (CRYSTAL FORM-2, CO-CRYSTALLIZATION)

OverviewOverview

The Ser/Thr protein kinase MAPKAP kinase 2 (MK2) plays a crucial role in, inflammation. We determined the structure of the kinase domain of MK2 in, complex with a low molecular mass inhibitor in two different crystal, forms, obtained from soaking and co-crystallization. To our knowledge, these are the first structures of MK2 showing the binding mode of an, inhibitor with high binding affinity (IC50 8.5 nM). The two crystal forms, revealed conformational flexibility in the binding site and extend the, experimental basis for rational drug design. Crystal form-1 contained one, MK2 molecule per asymmetric unit. Form-2 contained 12 molecules, which, arrange into two different types of MK2 trimers. One of them may serve as, a model for an intermediate state during substrate phosphorylation, as, each MK2 monomer places its activation segment into the substrate peptide, binding groove of the trimer neighbor.

About this StructureAbout this Structure

2JBP is a Single protein structure of sequence from Homo sapiens with as ligand. Active as Transferase, with EC number 2.7.11.1 Known structural/functional Sites: , , , , , , , , , and . Full crystallographic information is available from OCA.

ReferenceReference

Structural basis for a high affinity inhibitor bound to protein kinase MK2., Hillig RC, Eberspaecher U, Monteclaro F, Huber M, Nguyen D, Mengel A, Muller-Tiemann B, Egner U, J Mol Biol. 2007 Jun 8;369(3):735-45. Epub 2007 Mar 12. PMID:17449059

Page seeded by OCA on Wed Jan 23 11:12:51 2008

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OCA

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-[[Image:2jbp.jpg|left|200px]]<br /><applet load="2jbp" size="450" color="white" frame="true" align="right" spinBox="true"
+[[Image:2jbp.jpg|left|200px]]<br /><applet load="2jbp" size="350" color="white" frame="true" align="right" spinBox="true"
 caption="2jbp, resolution 3.31&Aring;" />
 '''PROTEIN KINASE MK2 IN COMPLEX WITH AN INHIBITOR (CRYSTAL FORM-2, CO-CRYSTALLIZATION)'''<br />
+==Overview==
+The Ser/Thr protein kinase MAPKAP kinase 2 (MK2) plays a crucial role in, inflammation. We determined the structure of the kinase domain of MK2 in, complex with a low molecular mass inhibitor in two different crystal, forms, obtained from soaking and co-crystallization. To our knowledge, these are the first structures of MK2 showing the binding mode of an, inhibitor with high binding affinity (IC50 8.5 nM). The two crystal forms, revealed conformational flexibility in the binding site and extend the, experimental basis for rational drug design. Crystal form-1 contained one, MK2 molecule per asymmetric unit. Form-2 contained 12 molecules, which, arrange into two different types of MK2 trimers. One of them may serve as, a model for an intermediate state during substrate phosphorylation, as, each MK2 monomer places its activation segment into the substrate peptide, binding groove of the trimer neighbor.
 ==About this Structure==
-JBP is a [http://en.wikipedia.org/wiki/Single_protein Single protein] structure of sequence from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens] with P4O 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] Known structural/functional Site: <scene name='pdbsite=AC1:P4o Binding Site For Chain L'>AC1</scene>. Full crystallographic information is available from [http://ispc.weizmann.ac.il/oca-bin/ocashort?id=2JBP OCA].
+JBP is a [http://en.wikipedia.org/wiki/Single_protein Single protein] structure of sequence from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens] with <scene name='pdbligand=P4O:'>P4O</scene> as [http://en.wikipedia.org/wiki/ligand ligand]. Active as [http://en.wikipedia.org/wiki/Transferase Transferase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=2.7.11.1 2.7.11.1] Known structural/functional Sites: <scene name='pdbsite=AC1:P4o Binding Site For Chain A'>AC1</scene>, <scene name='pdbsite=AC2:P4o Binding Site For Chain B'>AC2</scene>, <scene name='pdbsite=AC3:P4o Binding Site For Chain C'>AC3</scene>, <scene name='pdbsite=AC4:P4o Binding Site For Chain D'>AC4</scene>, <scene name='pdbsite=AC5:P4o Binding Site For Chain E'>AC5</scene>, <scene name='pdbsite=AC6:P4o Binding Site For Chain F'>AC6</scene>, <scene name='pdbsite=AC7:P4o Binding Site For Chain G'>AC7</scene>, <scene name='pdbsite=AC8:P4o Binding Site For Chain H'>AC8</scene>, <scene name='pdbsite=AC9:P4o Binding Site For Chain I'>AC9</scene>, <scene name='pdbsite=BC1:P4o Binding Site For Chain K'>BC1</scene> and <scene name='pdbsite=BC2:P4o Binding Site For Chain L'>BC2</scene>. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2JBP OCA].
+==Reference==
+Structural basis for a high affinity inhibitor bound to protein kinase MK2., Hillig RC, Eberspaecher U, Monteclaro F, Huber M, Nguyen D, Mengel A, Muller-Tiemann B, Egner U, J Mol Biol. 2007 Jun 8;369(3):735-45. Epub 2007 Mar 12. PMID:[http://ispc.weizmann.ac.il//pmbin/getpm?pmid=17449059 17449059]
 [[Category: Homo sapiens]]
-[[Category: Non-specific serine/threonine protein kinase]]
 [[Category: Single protein]]
+[[Category: Transferase]]
 [[Category: Eberspaecher, U.]]
 [[Category: Egner, U.]]
@@ Line 17: / Line 23: @@
 [[Category: Nguyen, D.]]
 [[Category: P4O]]
+[[Category: atp binding]]
 [[Category: atp site]]
-[[Category: atp-binding]]
 [[Category: co-crystallization]]
 [[Category: kinase]]
@@ Line 30: / Line 36: @@
 [[Category: transferase]]
-''Page seeded by [http://ispc.weizmann.ac.il/oca OCA ] on Tue Dec 18 19:59:09 2007''
+''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Wed Jan 23 11:12:51 2008''