4ehr

From Proteopedia

(Difference between revisions)
Jump to: navigation, search
Current revision (11:03, 1 March 2024) (edit) (undo)
 
Line 4: Line 4:
== Structural highlights ==
== Structural highlights ==
<table><tr><td colspan='2'>[[4ehr]] 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=4EHR OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=4EHR FirstGlance]. <br>
<table><tr><td colspan='2'>[[4ehr]] 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=4EHR OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=4EHR FirstGlance]. <br>
-
</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=0Q5:4-[5-BUTYL-3-(HYDROXYMETHYL)-1-PHENYL-1H-PYRAZOL-4-YL]-3-(3,4-DIHYDROISOQUINOLIN-2(1H)-YLCARBONYL)-N-{[2-(TRIMETHYLSILYL)ETHYL]SULFONYL}BENZAMIDE'>0Q5</scene>, <scene name='pdbligand=IMD:IMIDAZOLE'>IMD</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]] 2.09&#8491;</td></tr>
 +
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=0Q5:4-[5-BUTYL-3-(HYDROXYMETHYL)-1-PHENYL-1H-PYRAZOL-4-YL]-3-(3,4-DIHYDROISOQUINOLIN-2(1H)-YLCARBONYL)-N-{[2-(TRIMETHYLSILYL)ETHYL]SULFONYL}BENZAMIDE'>0Q5</scene>, <scene name='pdbligand=IMD:IMIDAZOLE'>IMD</scene></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=4ehr FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4ehr OCA], [https://pdbe.org/4ehr PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=4ehr RCSB], [https://www.ebi.ac.uk/pdbsum/4ehr PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=4ehr ProSAT]</span></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=4ehr FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4ehr OCA], [https://pdbe.org/4ehr PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=4ehr RCSB], [https://www.ebi.ac.uk/pdbsum/4ehr PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=4ehr ProSAT]</span></td></tr>
</table>
</table>
== Function ==
== Function ==
-
[[https://www.uniprot.org/uniprot/B2CL1_HUMAN B2CL1_HUMAN]] Potent inhibitor of cell death. Inhibits activation of caspases (By similarity). Appears to regulate cell death by blocking the voltage-dependent anion channel (VDAC) by binding to it and preventing the release of the caspase activator, CYC1, from the mitochondrial membrane. Also acts as a regulator of G2 checkpoint and progression to cytokinesis during mitosis.<ref>PMID:19917720</ref> <ref>PMID:21840391</ref> Isoform Bcl-X(S) promotes apoptosis.<ref>PMID:19917720</ref> <ref>PMID:21840391</ref>
+
[https://www.uniprot.org/uniprot/B2CL1_HUMAN B2CL1_HUMAN] Potent inhibitor of cell death. Inhibits activation of caspases (By similarity). Appears to regulate cell death by blocking the voltage-dependent anion channel (VDAC) by binding to it and preventing the release of the caspase activator, CYC1, from the mitochondrial membrane. Also acts as a regulator of G2 checkpoint and progression to cytokinesis during mitosis.<ref>PMID:19917720</ref> <ref>PMID:21840391</ref> Isoform Bcl-X(S) promotes apoptosis.<ref>PMID:19917720</ref> <ref>PMID:21840391</ref>
-
<div style="background-color:#fffaf0;">
+
-
== Publication Abstract from PubMed ==
+
-
5-Butyl-1,4-diphenyl pyrazole and 2-amino-5-chloro pyrimidine acylsulfonamides were developed as potent dual antagonists of Bcl-2 and Bcl-xL. Compounds were optimized for binding to the I88, L92, I95, and F99 pockets normally occupied by pro-apoptotic protein Bim. An X-ray crystal structure confirmed the proposed binding mode. Observation of cytochrome c release from isolated mitochondria in MV-411 cells provides further evidence of target inhibition. Compounds demonstrated submicromolar antiproliferative activity in Bcl-2/Bcl-xL dependent cell lines.
+
-
 
+
-
Pyrazole and pyrimidine phenylacylsulfonamides as dual Bcl-2/Bcl-xL antagonists.,Schroeder GM, Wei D, Banfi P, Cai ZW, Lippy J, Menichincheri M, Modugno M, Naglich J, Penhallow B, Perez HL, Sack J, Schmidt RJ, Tebben A, Yan C, Zhang L, Galvani A, Lombardo LJ, Borzilleri RM Bioorg Med Chem Lett. 2012 Jun 15;22(12):3951-6. Epub 2012 Apr 30. PMID:22608393<ref>PMID:22608393</ref>
+
-
 
+
-
From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
+
-
</div>
+
-
<div class="pdbe-citations 4ehr" style="background-color:#fffaf0;"></div>
+
==See Also==
==See Also==

Current revision

Crystal structure of Bcl-Xl complex with 4-(5-butyl-3-(hydroxymethyl)-1-phenyl-1h-pyrazol-4-yl)-3-(3,4-dihydro-2(1h)-isoquinolinylcarbonyl)-n-((2-(trimethylsilyl)ethyl)sulfonyl)benzamide

PDB ID 4ehr

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/4ehr"
Personal tools