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[[ | ==Human p38 MAP kinase in complex with NP-F11 and RL87== | ||
<StructureSection load='4eh9' size='340' side='right' caption='[[4eh9]], [[Resolution|resolution]] 2.10Å' scene=''> | |||
== Structural highlights == | |||
<table><tr><td colspan='2'>[[4eh9]] is a 1 chain structure with sequence from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4EH9 OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4EH9 FirstGlance]. <br> | |||
</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=0OQ:(1R,5S)-3-[4-(TRIFLUOROMETHYL)BENZOYL]-1,2,3,4,5,6-HEXAHYDRO-8H-1,5-METHANOPYRIDO[1,2-A][1,5]DIAZOCIN-8-ONE'>0OQ</scene>, <scene name='pdbligand=IRG:N~4~-CYCLOPROPYL-2-PHENYLQUINAZOLINE-4,7-DIAMINE'>IRG</scene></td></tr> | |||
<tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[4eh2|4eh2]], [[4eh3|4eh3]], [[4eh4|4eh4]], [[4eh5|4eh5]], [[4eh6|4eh6]], [[4eh7|4eh7]], [[4eh8|4eh8]]</td></tr> | |||
<tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">MAPK14, CSBP, CSBP1, CSBP2, CSPB1, MXI2, SAPK2A ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 Homo sapiens])</td></tr> | |||
<tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[http://en.wikipedia.org/wiki/Mitogen-activated_protein_kinase Mitogen-activated protein kinase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=2.7.11.24 2.7.11.24] </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=4eh9 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4eh9 OCA], [http://www.rcsb.org/pdb/explore.do?structureId=4eh9 RCSB], [http://www.ebi.ac.uk/pdbsum/4eh9 PDBsum]</span></td></tr> | |||
</table> | |||
<div style="background-color:#fffaf0;"> | |||
== Publication Abstract from PubMed == | |||
Fragment-based ligand and drug discovery predominantly employs sp(2)-rich compounds covering well-explored regions of chemical space. Despite the ease with which such fragments can be coupled, this focus on flat compounds is widely cited as contributing to the attrition rate of the drug discovery process. In contrast, biologically validated natural products are rich in stereogenic centres and populate areas of chemical space not occupied by average synthetic molecules. Here, we have analysed more than 180,000 natural product structures to arrive at 2,000 clusters of natural-product-derived fragments with high structural diversity, which resemble natural scaffolds and are rich in sp(3)-configured centres. The structures of the cluster centres differ from previously explored fragment libraries, but for nearly half of the clusters representative members are commercially available. We validate their usefulness for the discovery of novel ligand and inhibitor types by means of protein X-ray crystallography and the identification of novel stabilizers of inactive conformations of p38alpha MAP kinase and of inhibitors of several phosphatases. | |||
Natural-product-derived fragments for fragment-based ligand discovery.,Over B, Wetzel S, Grutter C, Nakai Y, Renner S, Rauh D, Waldmann H Nat Chem. 2012 Dec 18;5(1):21-8. doi: 10.1038/nchem.1506. Epub 2012 Dec 2. PMID:23247173<ref>PMID:23247173</ref> | |||
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | |||
</div> | |||
==See Also== | |||
*[[Mitogen-activated protein kinase|Mitogen-activated protein kinase]] | |||
== | == References == | ||
[[ | <references/> | ||
__TOC__ | |||
</StructureSection> | |||
[[Category: Homo sapiens]] | [[Category: Homo sapiens]] | ||
[[Category: Mitogen-activated protein kinase]] | [[Category: Mitogen-activated protein kinase]] | ||
[[Category: Gruetter, C | [[Category: Gruetter, C]] | ||
[[Category: Over, B | [[Category: Over, B]] | ||
[[Category: Rauh, D | [[Category: Rauh, D]] | ||
[[Category: Waldmann, H | [[Category: Waldmann, H]] | ||
[[Category: Allosteric pocket]] | [[Category: Allosteric pocket]] | ||
[[Category: Kinase-ligand complex]] | [[Category: Kinase-ligand complex]] | ||
[[Category: Map kinase insert]] | [[Category: Map kinase insert]] | ||
[[Category: Transferase-transferase inhibitor complex]] | [[Category: Transferase-transferase inhibitor complex]] | ||
Revision as of 19:41, 9 December 2014
Human p38 MAP kinase in complex with NP-F11 and RL87Human p38 MAP kinase in complex with NP-F11 and RL87
Structural highlights
Publication Abstract from PubMedFragment-based ligand and drug discovery predominantly employs sp(2)-rich compounds covering well-explored regions of chemical space. Despite the ease with which such fragments can be coupled, this focus on flat compounds is widely cited as contributing to the attrition rate of the drug discovery process. In contrast, biologically validated natural products are rich in stereogenic centres and populate areas of chemical space not occupied by average synthetic molecules. Here, we have analysed more than 180,000 natural product structures to arrive at 2,000 clusters of natural-product-derived fragments with high structural diversity, which resemble natural scaffolds and are rich in sp(3)-configured centres. The structures of the cluster centres differ from previously explored fragment libraries, but for nearly half of the clusters representative members are commercially available. We validate their usefulness for the discovery of novel ligand and inhibitor types by means of protein X-ray crystallography and the identification of novel stabilizers of inactive conformations of p38alpha MAP kinase and of inhibitors of several phosphatases. Natural-product-derived fragments for fragment-based ligand discovery.,Over B, Wetzel S, Grutter C, Nakai Y, Renner S, Rauh D, Waldmann H Nat Chem. 2012 Dec 18;5(1):21-8. doi: 10.1038/nchem.1506. Epub 2012 Dec 2. PMID:23247173[1] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See AlsoReferences
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