4hw2

From Proteopedia

(Difference between revisions)
Jump to: navigation, search
Current revision (11:45, 1 March 2024) (edit) (undo)
 
(3 intermediate revisions not shown.)
Line 1: Line 1:
 +
==Discovery of potent Mcl-1 inhibitors using fragment-based methods and structure-based design==
==Discovery of potent Mcl-1 inhibitors using fragment-based methods and structure-based design==
-
<StructureSection load='4hw2' size='340' side='right' caption='[[4hw2]], [[Resolution|resolution]] 2.80&Aring;' scene=''>
+
<StructureSection load='4hw2' size='340' side='right'caption='[[4hw2]], [[Resolution|resolution]] 2.80&Aring;' scene=''>
== Structural highlights ==
== Structural highlights ==
-
<table><tr><td colspan='2'>[[4hw2]] is a 6 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=4HW2 OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4HW2 FirstGlance]. <br>
+
<table><tr><td colspan='2'>[[4hw2]] is a 6 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=4HW2 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=4HW2 FirstGlance]. <br>
-
</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=19H:6-CHLORO-3-[3-(4-CHLORO-3,5-DIMETHYLPHENOXY)PROPYL]-1H-INDOLE-2-CARBOXYLIC+ACID'>19H</scene>, <scene name='pdbligand=EDO:1,2-ETHANEDIOL'>EDO</scene>, <scene name='pdbligand=PGE:TRIETHYLENE+GLYCOL'>PGE</scene></td></tr>
+
</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 2.8&#8491;</td></tr>
-
<tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[4hw3|4hw3]], [[4hw4|4hw4]]</td></tr>
+
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=19H:6-CHLORO-3-[3-(4-CHLORO-3,5-DIMETHYLPHENOXY)PROPYL]-1H-INDOLE-2-CARBOXYLIC+ACID'>19H</scene>, <scene name='pdbligand=EDO:1,2-ETHANEDIOL'>EDO</scene>, <scene name='pdbligand=PGE:TRIETHYLENE+GLYCOL'>PGE</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 Homo sapiens])</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=4hw2 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4hw2 OCA], [https://pdbe.org/4hw2 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=4hw2 RCSB], [https://www.ebi.ac.uk/pdbsum/4hw2 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=4hw2 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=4hw2 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4hw2 OCA], [http://www.rcsb.org/pdb/explore.do?structureId=4hw2 RCSB], [http://www.ebi.ac.uk/pdbsum/4hw2 PDBsum]</span></td></tr>
+
</table>
</table>
-
<div style="background-color:#fffaf0;">
+
== Function ==
-
== Publication Abstract from PubMed ==
+
[https://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>
-
Myeloid cell leukemia 1 (Mcl-1), a member of the Bcl-2 family of proteins, is overexpressed and amplified in various cancers and promotes the aberrant survival of tumor cells that otherwise would undergo apoptosis. Here we describe the discovery of potent and selective Mcl-1 inhibitors using fragment-based methods and structure-based design. NMR-based screening of a large fragment library identified two chemically distinct hit series that bind to different sites on Mcl-1. Members of the two fragment classes were merged together to produce lead compounds that bind to Mcl-1 with a dissociation constant of &lt;100 nM with selectivity for Mcl-1 over Bcl-xL and Bcl-2. Structures of merged compounds when complexed to Mcl-1 were obtained by X-ray crystallography and provide detailed information about the molecular recognition of small-molecule ligands binding Mcl-1. The compounds represent starting points for the discovery of clinically useful Mcl-1 inhibitors for the treatment of a wide variety of cancers.
+
-
 
+
-
Discovery of Potent Myeloid Cell Leukemia 1 (Mcl-1) Inhibitors Using Fragment-Based Methods and Structure-Based Design.,Friberg A, Vigil D, Zhao B, Daniels RN, Burke JP, Garcia-Barrantes PM, Camper D, Chauder BA, Lee T, Olejniczak ET, Fesik SW J Med Chem. 2012 Dec 17. PMID:23244564<ref>PMID:23244564</ref>
+
-
From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
+
==See Also==
-
</div>
+
*[[B-cell lymphoma proteins 3D structures|B-cell lymphoma proteins 3D structures]]
== References ==
== References ==
<references/>
<references/>
Line 21: Line 18:
</StructureSection>
</StructureSection>
[[Category: Homo sapiens]]
[[Category: Homo sapiens]]
-
[[Category: Zhao, B]]
+
[[Category: Large Structures]]
-
[[Category: Apoptosis]]
+
[[Category: Zhao B]]
-
[[Category: Apoptosis-inhibitor complex]]
+
-
[[Category: Maintenance of viability]]
+
-
[[Category: Regulation of apoptosis]]
+

Current revision

Discovery of potent Mcl-1 inhibitors using fragment-based methods and structure-based design

PDB ID 4hw2

Drag the structure with the mouse to rotate

Proteopedia Page Contributors and Editors (what is this?)

OCA

Retrieved from "http://52.214.119.220/wiki/index.php/4hw2"
Personal tools