6p3p
From Proteopedia
(Difference between revisions)
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<StructureSection load='6p3p' size='340' side='right'caption='[[6p3p]], [[Resolution|resolution]] 1.61Å' scene=''> | <StructureSection load='6p3p' size='340' side='right'caption='[[6p3p]], [[Resolution|resolution]] 1.61Å' scene=''> | ||
== Structural highlights == | == Structural highlights == | ||
| - | <table><tr><td colspan='2'>[[6p3p]] is a 1 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6P3P OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=6P3P FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[6p3p]] is a 1 chain structure with sequence from [http://en.wikipedia.org/wiki/Human Human]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6P3P OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=6P3P FirstGlance]. <br> |
</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=NQJ:methyl+N-(5-{[2-chloro-5-(trifluoromethyl)phenyl]sulfamoyl}-4-methylthiophene-2-carbonyl)-D-phenylalaninate'>NQJ</scene></td></tr> | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=NQJ:methyl+N-(5-{[2-chloro-5-(trifluoromethyl)phenyl]sulfamoyl}-4-methylthiophene-2-carbonyl)-D-phenylalaninate'>NQJ</scene></td></tr> | ||
| + | <tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">MCL1, BCL2L3 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN])</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=6p3p FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6p3p OCA], [http://pdbe.org/6p3p PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=6p3p RCSB], [http://www.ebi.ac.uk/pdbsum/6p3p PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=6p3p ProSAT]</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=6p3p FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6p3p OCA], [http://pdbe.org/6p3p PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=6p3p RCSB], [http://www.ebi.ac.uk/pdbsum/6p3p PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=6p3p ProSAT]</span></td></tr> | ||
</table> | </table> | ||
== Function == | == Function == | ||
[[http://www.uniprot.org/uniprot/MCL1_HUMAN MCL1_HUMAN]] Involved in the regulation of apoptosis versus cell survival, and in the maintenance of viability but not of proliferation. Mediates its effects by interactions with a number of other regulators of apoptosis. Isoform 1 inhibits apoptosis. Isoform 2 promotes apoptosis.<ref>PMID:10766760</ref> | [[http://www.uniprot.org/uniprot/MCL1_HUMAN MCL1_HUMAN]] Involved in the regulation of apoptosis versus cell survival, and in the maintenance of viability but not of proliferation. Mediates its effects by interactions with a number of other regulators of apoptosis. Isoform 1 inhibits apoptosis. Isoform 2 promotes apoptosis.<ref>PMID:10766760</ref> | ||
| + | <div style="background-color:#fffaf0;"> | ||
| + | == Publication Abstract from PubMed == | ||
| + | Mcl-1 is an anti-apoptotic protein overexpressed in hematological malignancies and several human solid tumors. Small molecule inhibition of Mcl-1 would offer an effective therapy to Mcl-1 mediated resistance. Subsequently, it has been the target of extensive research in the pharmaceutical industry. The discovery of a novel class of Mcl-1 small molecule inhibitors is described beginning with a simple biaryl sulfonamide hit derived from a high through put screen. A medicinal chemistry effort aided by SBDD generated compounds capable of disrupting the Mcl-1/Bid protein-protein interaction in vitro. The crystal structure of the Mcl-1 bound ligand represents a unique binding mode to the BH3 binding pocket where binding affinity is achieved, in part, through a sulfonamide oxygen/Arg263 interaction. The work highlights the some of the key challenges in designing effective protein-protein inhibitors for the Bcl-2 class of proteins. | ||
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| + | Discovery of novel biaryl sulfonamide based Mcl-1 inhibitors.,Follows B, Fessler S, Baumeister T, Campbell AM, Zablocki MM, Li H, Gotur D, Wang Z, Zheng X, Molz L, Nguyen C, Herbertz T, Wang L, Bair K Bioorg Med Chem Lett. 2019 Jun 11. pii: S0960-894X(19)30375-0. doi:, 10.1016/j.bmcl.2019.06.008. PMID:31235261<ref>PMID:31235261</ref> | ||
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| + | From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | ||
| + | </div> | ||
| + | <div class="pdbe-citations 6p3p" style="background-color:#fffaf0;"></div> | ||
== References == | == References == | ||
<references/> | <references/> | ||
__TOC__ | __TOC__ | ||
</StructureSection> | </StructureSection> | ||
| + | [[Category: Human]] | ||
[[Category: Large Structures]] | [[Category: Large Structures]] | ||
[[Category: Follows, B]] | [[Category: Follows, B]] | ||
Revision as of 06:36, 10 July 2019
Crystal structure of Mcl-1 in complex with compound 65
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