This old version of Proteopedia is provided for student assignments while the new version is undergoing repairs. Content and edits done in this old version of Proteopedia after March 1, 2026 will eventually be lost when it is retired in about June of 2026.
Apply for new accounts at the new Proteopedia. Your logins will work in both the old and new versions.
4qtb
From Proteopedia
(Difference between revisions)
| Line 8: | Line 8: | ||
<tr><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4qtb FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4qtb OCA], [http://www.rcsb.org/pdb/explore.do?structureId=4qtb RCSB], [http://www.ebi.ac.uk/pdbsum/4qtb PDBsum]</span></td></tr> | <tr><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4qtb FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4qtb OCA], [http://www.rcsb.org/pdb/explore.do?structureId=4qtb RCSB], [http://www.ebi.ac.uk/pdbsum/4qtb PDBsum]</span></td></tr> | ||
<table> | <table> | ||
| + | <div style="background-color:#fffaf0;"> | ||
| + | == Publication Abstract from PubMed == | ||
| + | Activation of the ERK pathway is a hallmark of cancer, and targeting of upstream signaling partners led to the development of approved drugs. Recently, SCH772984 has been shown to be a selective and potent ERK1/2 inhibitor. Here we report the structural mechanism for its remarkable selectivity. In ERK1/2, SCH772984 induces a so-far-unknown binding pocket that accommodates the piperazine-phenyl-pyrimidine decoration. This new binding pocket was created by an inactive conformation of the phosphate-binding loop and an outward tilt of helix alphaC. In contrast, structure determination of SCH772984 with the off-target haspin and JNK1 revealed two canonical but distinct type I binding modes. Notably, the new binding mode with ERK1/2 was associated with slow binding kinetics in vitro as well as in cell-based assay systems. The described binding mode of SCH772984 with ERK1/2 enables the design of a new type of specific kinase inhibitors with prolonged on-target activity. | ||
| + | |||
| + | A unique inhibitor binding site in ERK1/2 is associated with slow binding kinetics.,Chaikuad A, M C Tacconi E, Zimmer J, Liang Y, Gray NS, Tarsounas M, Knapp S Nat Chem Biol. 2014 Oct;10(10):853-60. doi: 10.1038/nchembio.1629. Epub 2014 Sep , 7. PMID:25195011<ref>PMID:25195011</ref> | ||
| + | |||
| + | From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | ||
| + | </div> | ||
| + | == References == | ||
| + | <references/> | ||
__TOC__ | __TOC__ | ||
</StructureSection> | </StructureSection> | ||
Revision as of 07:15, 24 September 2014
Structure of human ERK1 in complex with SCH772984 revealing a novel inhibitor-induced binding pocket
| |||||||||||
Categories: Mitogen-activated protein kinase | Arrowsmith, C H. | Bountra, C. | Chaikuad, A. | Delft, F von. | Edwards, A M. | Keates, T. | Knapp, S. | SGC, Structural Genomics Consortium. | Allosteric | Inhibitor | Kinase | Mapk | Sgc | Signalling | Structural genomic | Structural genomics consortium | Transferase | Transferase-transferase inhibitor complex
