1wbt

From Proteopedia

(Difference between revisions)

Revision as of 06:33, 31 January 2018

Identification of novel p38 alpha MAP Kinase inhibitors using fragment-based lead generation.

Structural highlights

1wbt is a 1 chain structure with sequence from Human. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Ligands:
Related:	1a9u, 1bl6, 1bl7, 1bmk, 1di9, 1ian, 1kv1, 1kv2, 1m7q, 1ouk, 1ouy, 1ove, 1oz1, 1r39, 1r3c, 1w7h, 1w82, 1w83, 1w84, 1wbn, 1wbo, 1wbs, 1wbv, 1wbw, 1wfc, 1yqj, 1zz2, 1zzl
Activity:	Transferase, with EC number 2.7.11.8, 2.7.11.9, 2.7.11.10, 2.7.11.11, 2.7.11.12, 2.7.11.13, 2.7.11.21, 2.7.11.22, 2.7.11.24, 2.7.11.25, 2.7.11.30 and 2.7.12.1 2.7.11.1, 2.7.11.8, 2.7.11.9, 2.7.11.10, 2.7.11.11, 2.7.11.12, 2.7.11.13, 2.7.11.21, 2.7.11.22, 2.7.11.24, 2.7.11.25, 2.7.11.30 and 2.7.12.1
Resources:	FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Evolutionary Conservation

Check, as determined by ConSurfDB. You may read the explanation of the method and the full data available from ConSurf.

Publication Abstract from PubMed

We describe the structure-guided optimization of the molecular fragments 2-amino-3-benzyloxypyridine 1 (IC(50) 1.3 mM) and 3-(2-(4-pyridyl)ethyl)indole 2 (IC(50) 35 microM) identified using X-ray crystallographic screening of p38alpha MAP kinase. Using two separate case studies, the article focuses on the key compounds synthesized, the structure-activity relationships and the binding mode observations made during this optimization process, resulting in two potent lead series that demonstrate significant increases in activity. We describe the process of compound elaboration either through the growing out from fragments into adjacent pockets or through the conjoining of overlapping fragments and demonstrate that we have exploited the mobile conserved activation loop, consisting in part of Asp168-Phe169-Gly170 (DFG), to generate significant improvements in potency and kinase selectivity.

Identification of novel p38alpha MAP kinase inhibitors using fragment-based lead generation.,Gill AL, Frederickson M, Cleasby A, Woodhead SJ, Carr MG, Woodhead AJ, Walker MT, Congreve MS, Devine LA, Tisi D, O'Reilly M, Seavers LC, Davis DJ, Curry J, Anthony R, Padova A, Murray CW, Carr RA, Jhoti H J Med Chem. 2005 Jan 27;48(2):414-26. PMID:15658855^[1]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

References

↑ Gill AL, Frederickson M, Cleasby A, Woodhead SJ, Carr MG, Woodhead AJ, Walker MT, Congreve MS, Devine LA, Tisi D, O'Reilly M, Seavers LC, Davis DJ, Curry J, Anthony R, Padova A, Murray CW, Carr RA, Jhoti H. Identification of novel p38alpha MAP kinase inhibitors using fragment-based lead generation. J Med Chem. 2005 Jan 27;48(2):414-26. PMID:15658855 doi:10.1021/jm049575n

1 Structural highlights
2 Evolutionary Conservation
3 Publication Abstract from PubMed
4 References

Proteopedia Page Contributors and Editors (what is this?)

OCA

Retrieved from "http://52.214.119.220/wiki/index.php/1wbt"

@@ Line 1: / Line 1: @@
-==IDENTIFICATION OF NOVEL P38 ALPHA MAP KINASE INHIBITORS USING FRAGMENT-BASED LEAD GENERATION.==
+==Identification of novel p38 alpha MAP Kinase inhibitors using fragment-based lead generation.==
 <StructureSection load='1wbt' size='340' side='right' caption='[[1wbt]], [[Resolution|resolution]] 2.00&Aring;' scene=''>
 == Structural highlights ==
@@ Line 6: / Line 7: @@
 <tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[1a9u|1a9u]], [[1bl6|1bl6]], [[1bl7|1bl7]], [[1bmk|1bmk]], [[1di9|1di9]], [[1ian|1ian]], [[1kv1|1kv1]], [[1kv2|1kv2]], [[1m7q|1m7q]], [[1ouk|1ouk]], [[1ouy|1ouy]], [[1ove|1ove]], [[1oz1|1oz1]], [[1r39|1r39]], [[1r3c|1r3c]], [[1w7h|1w7h]], [[1w82|1w82]], [[1w83|1w83]], [[1w84|1w84]], [[1wbn|1wbn]], [[1wbo|1wbo]], [[1wbs|1wbs]], [[1wbv|1wbv]], [[1wbw|1wbw]], [[1wfc|1wfc]], [[1yqj|1yqj]], [[1zz2|1zz2]], [[1zzl|1zzl]]</td></tr>
 <tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[http://en.wikipedia.org/wiki/Transferase Transferase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=2.7.11.1, 2.7.11.8, 2.7.11.9, 2.7.11.10, 2.7.11.11, 2.7.11.12, 2.7.11.13, 2.7.11.21, 2.7.11.22, 2.7.11.24, 2.7.11.25, 2.7.11.30 and 2.7.12.1 2.7.11.1, 2.7.11.8, 2.7.11.9, 2.7.11.10, 2.7.11.11, 2.7.11.12, 2.7.11.13, 2.7.11.21, 2.7.11.22, 2.7.11.24, 2.7.11.25, 2.7.11.30 and 2.7.12.1] </span></td></tr>
-<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=1wbt FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1wbt OCA], [http://pdbe.org/1wbt PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=1wbt RCSB], [http://www.ebi.ac.uk/pdbsum/1wbt PDBsum]</span></td></tr>
+<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=1wbt FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1wbt OCA], [http://pdbe.org/1wbt PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=1wbt RCSB], [http://www.ebi.ac.uk/pdbsum/1wbt PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=1wbt ProSAT]</span></td></tr>
 </table>
 == Evolutionary Conservation ==
@@ Line 12: / Line 13: @@
 Check<jmol>
   <jmolCheckbox>
-    <scriptWhenChecked>select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/wb/1wbt_consurf.spt"</scriptWhenChecked>
+    <scriptWhenChecked>; select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/wb/1wbt_consurf.spt"</scriptWhenChecked>
     <scriptWhenUnchecked>script /wiki/extensions/Proteopedia/spt/initialview01.spt</scriptWhenUnchecked>
     <text>to colour the structure by Evolutionary Conservation</text>
   </jmolCheckbox>
-</jmol>, as determined by [http://consurfdb.tau.ac.il/ ConSurfDB]. You may read the [[Conservation%2C_Evolutionary|explanation]] of the method and the full data available from [http://bental.tau.ac.il/new_ConSurfDB/chain_selection.php?pdb_ID=2ata ConSurf].
+</jmol>, as determined by [http://consurfdb.tau.ac.il/ ConSurfDB]. You may read the [[Conservation%2C_Evolutionary|explanation]] of the method and the full data available from [http://bental.tau.ac.il/new_ConSurfDB/main_output.php?pdb_ID=1wbt ConSurf].
 <div style="clear:both"></div>
 <div style="background-color:#fffaf0;">
@@ Line 27: / Line 28: @@
 </div>
 <div class="pdbe-citations 1wbt" style="background-color:#fffaf0;"></div>
-==See Also==
-*[[Mitogen-activated protein kinase|Mitogen-activated protein kinase]]
 == References ==
 <references/>

1wbt

From Proteopedia

Revision as of 06:33, 31 January 2018

Identification of novel p38 alpha MAP Kinase inhibitors using fragment-based lead generation.

Structural highlights

Evolutionary Conservation

Publication Abstract from PubMed

References

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Proteopedia Page Contributors and Editors (what is this?)

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