8zud
From Proteopedia
(Difference between revisions)
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| - | '''Unreleased structure''' | ||
| - | + | ==Crystal Structure of Human Myt1 Kinase domain Bounded with compound 8f== | |
| + | <StructureSection load='8zud' size='340' side='right'caption='[[8zud]], [[Resolution|resolution]] 1.51Å' scene=''> | ||
| + | == Structural highlights == | ||
| + | <table><tr><td colspan='2'>[[8zud]] is a 1 chain structure with sequence from [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=8ZUD OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=8ZUD FirstGlance]. <br> | ||
| + | </td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 1.5051008Å</td></tr> | ||
| + | <tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=8zud FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=8zud OCA], [https://pdbe.org/8zud PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=8zud RCSB], [https://www.ebi.ac.uk/pdbsum/8zud PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=8zud ProSAT]</span></td></tr> | ||
| + | </table> | ||
| + | == Function == | ||
| + | [https://www.uniprot.org/uniprot/PMYT1_HUMAN PMYT1_HUMAN] Acts as a negative regulator of entry into mitosis (G2 to M transition) by phosphorylation of the CDK1 kinase specifically when CDK1 is complexed to cyclins. Mediates phosphorylation of CDK1 predominantly on 'Thr-14'. Also involved in Golgi fragmentation. May be involved in phosphorylation of CDK1 on 'Tyr-15' to a lesser degree, however tyrosine kinase activity is unclear and may be indirect. May be a downstream target of Notch signaling pathway during eye development.<ref>PMID:9001210</ref> <ref>PMID:10373560</ref> | ||
| + | <div style="background-color:#fffaf0;"> | ||
| + | == Publication Abstract from PubMed == | ||
| + | CCNE1 amplification occurs in breast cancer and currently lacks effective therapies. PKMYT1 as a synthetic lethal target for CCNE1 amplification holds promise for the treatment of CCNE1-amplified breast cancer. Herein, we discover a series of 2-amino-[1,1'-biphenyl]-3-carboxamide derivatives as potent and selective PKMYT1 inhibitors using structure-based drug design. The representative compound 8ma exhibited excellent potency against PKMYT1, while sparing WEE1. It also suppressed proliferation of the CCNE1-amplified HCC1569 breast cancer cell line and showed synergistic cytotoxicity in combination with gemcitabine. PKMYT1 X-ray cocrystallography confirmed that introduction of key binding interactions between the inhibitors and residues Asp251 and Tyr121 of PKMYT1 greatly enhanced the potency and selectivity of the compounds. | ||
| - | + | Structure-Based Drug Design of 2-Amino-[1,1'-biphenyl]-3-carboxamide Derivatives as Selective PKMYT1 Inhibitors for the Treatment of CCNE1-Amplified Breast Cancer.,Wang C, Fang Y, Zhou Z, Liu Z, Feng F, Wan X, Li Y, Liu S, Ding J, Zhang ZM, Xie H, Lu X J Med Chem. 2024 Aug 20. doi: 10.1021/acs.jmedchem.4c01458. PMID:39163619<ref>PMID:39163619</ref> | |
| - | + | From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | |
| - | [[Category: | + | </div> |
| - | [[Category: | + | <div class="pdbe-citations 8zud" style="background-color:#fffaf0;"></div> |
| - | [[Category: Zhang | + | == References == |
| + | <references/> | ||
| + | __TOC__ | ||
| + | </StructureSection> | ||
| + | [[Category: Homo sapiens]] | ||
| + | [[Category: Large Structures]] | ||
| + | [[Category: Zhang ZM]] | ||
| + | [[Category: Zhou ZQ]] | ||
Current revision
Crystal Structure of Human Myt1 Kinase domain Bounded with compound 8f
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