4tuh

From Proteopedia

(Difference between revisions)

Current revision

Bcl-xL in complex with inhibitor (Compound 10)

Structural highlights

4tuh is a 8 chain structure with sequence from Homo sapiens. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Method:	X-ray diffraction, Resolution 1.8Å
Ligands:	, ,
Resources:	FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Function

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.^[1] ^[2] Isoform Bcl-X(S) promotes apoptosis.^[3] ^[4]

Publication Abstract from PubMed

Because of the promise of BCL-2 antagonists in combating chronic lymphocytic leukemia (CLL) and non-Hodgkin's lymphoma (NHL), interest in additional selective antagonists of antiapoptotic proteins has grown. Beginning with a series of selective, potent BCL-XL antagonists containing an undesirable hydrazone functionality, in silico design and X-ray crystallography were utilized to develop alternative scaffolds that retained the selectivity and potency of the starting compounds.

Structure-Guided Rescaffolding of Selective Antagonists of BCL-XL.,Koehler MF, Bergeron P, Choo EF, Lau K, Ndubaku C, Dudley D, Gibbons P, Sleebs BE, Rye CS, Nikolakopoulos G, Bui C, Kulasegaram S, Kersten WJ, Smith BJ, Czabotar PE, Colman PM, Huang DC, Baell JB, Watson KG, Hasvold L, Tao ZF, Wang L, Souers AJ, Elmore SW, Flygare JA, Fairbrother WJ, Lessene G ACS Med Chem Lett. 2014 Mar 21;5(6):662-7. doi: 10.1021/ml500030p. eCollection, 2014 Jun 12. PMID:24944740^[5]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

References

↑ Terrano DT, Upreti M, Chambers TC. Cyclin-dependent kinase 1-mediated Bcl-xL/Bcl-2 phosphorylation acts as a functional link coupling mitotic arrest and apoptosis. Mol Cell Biol. 2010 Feb;30(3):640-56. doi: 10.1128/MCB.00882-09. Epub 2009 Nov, 16. PMID:19917720 doi:10.1128/MCB.00882-09
↑ Wang J, Beauchemin M, Bertrand R. Bcl-xL phosphorylation at Ser49 by polo kinase 3 during cell cycle progression and checkpoints. Cell Signal. 2011 Dec;23(12):2030-8. doi: 10.1016/j.cellsig.2011.07.017. Epub, 2011 Aug 5. PMID:21840391 doi:10.1016/j.cellsig.2011.07.017
↑ Terrano DT, Upreti M, Chambers TC. Cyclin-dependent kinase 1-mediated Bcl-xL/Bcl-2 phosphorylation acts as a functional link coupling mitotic arrest and apoptosis. Mol Cell Biol. 2010 Feb;30(3):640-56. doi: 10.1128/MCB.00882-09. Epub 2009 Nov, 16. PMID:19917720 doi:10.1128/MCB.00882-09
↑ Wang J, Beauchemin M, Bertrand R. Bcl-xL phosphorylation at Ser49 by polo kinase 3 during cell cycle progression and checkpoints. Cell Signal. 2011 Dec;23(12):2030-8. doi: 10.1016/j.cellsig.2011.07.017. Epub, 2011 Aug 5. PMID:21840391 doi:10.1016/j.cellsig.2011.07.017
↑ Koehler MF, Bergeron P, Choo EF, Lau K, Ndubaku C, Dudley D, Gibbons P, Sleebs BE, Rye CS, Nikolakopoulos G, Bui C, Kulasegaram S, Kersten WJ, Smith BJ, Czabotar PE, Colman PM, Huang DC, Baell JB, Watson KG, Hasvold L, Tao ZF, Wang L, Souers AJ, Elmore SW, Flygare JA, Fairbrother WJ, Lessene G. Structure-Guided Rescaffolding of Selective Antagonists of BCL-XL. ACS Med Chem Lett. 2014 Mar 21;5(6):662-7. doi: 10.1021/ml500030p. eCollection, 2014 Jun 12. PMID:24944740 doi:http://dx.doi.org/10.1021/ml500030p

1 Structural highlights
2 Function
3 Publication Abstract from PubMed
4 See Also
5 References

Proteopedia Page Contributors and Editors (what is this?)

OCA

Retrieved from "http://52.214.119.220/wiki/index.php/4tuh"

@@ Line 1: / Line 1: @@
-'''Unreleased structure'''
-The entry 4tuh is ON HOLD  until Paper Publication
+==Bcl-xL in complex with inhibitor (Compound 10)==
+<StructureSection load='4tuh' size='340' side='right'caption='[[4tuh]], [[Resolution|resolution]] 1.80&Aring;' scene=''>
+== Structural highlights ==
+<table><tr><td colspan='2'>[[4tuh]] is a 8 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=4TUH OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=4TUH 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]] 1.8&#8491;</td></tr>
+<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=38H:2-[8-(1,3-BENZOTHIAZOL-2-YLCARBAMOYL)-3,4-DIHYDROISOQUINOLIN-2(1H)-YL]-5-{3-[4-(1H-PYRAZOLO[3,4-D]PYRIMIDIN-1-YL)PHENOXY]PROPYL}-1,3-THIAZOLE-4-CARBOXYLIC+ACID'>38H</scene>, <scene name='pdbligand=ACT:ACETATE+ION'>ACT</scene>, <scene name='pdbligand=EDO:1,2-ETHANEDIOL'>EDO</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=4tuh FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4tuh OCA], [https://pdbe.org/4tuh PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=4tuh RCSB], [https://www.ebi.ac.uk/pdbsum/4tuh PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=4tuh ProSAT]</span></td></tr>
+</table>
+== 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>
+<div style="background-color:#fffaf0;">
+== Publication Abstract from PubMed ==
+Because of the promise of BCL-2 antagonists in combating chronic lymphocytic leukemia (CLL) and non-Hodgkin's lymphoma (NHL), interest in additional selective antagonists of antiapoptotic proteins has grown. Beginning with a series of selective, potent BCL-XL antagonists containing an undesirable hydrazone functionality, in silico design and X-ray crystallography were utilized to develop alternative scaffolds that retained the selectivity and potency of the starting compounds.
-Authors: Czabotar, P.E., Lessense, G., Smith, B.J., Colman, P.M.
+Structure-Guided Rescaffolding of Selective Antagonists of BCL-XL.,Koehler MF, Bergeron P, Choo EF, Lau K, Ndubaku C, Dudley D, Gibbons P, Sleebs BE, Rye CS, Nikolakopoulos G, Bui C, Kulasegaram S, Kersten WJ, Smith BJ, Czabotar PE, Colman PM, Huang DC, Baell JB, Watson KG, Hasvold L, Tao ZF, Wang L, Souers AJ, Elmore SW, Flygare JA, Fairbrother WJ, Lessene G ACS Med Chem Lett. 2014 Mar 21;5(6):662-7. doi: 10.1021/ml500030p. eCollection, 2014 Jun 12. PMID:24944740<ref>PMID:24944740</ref>
-Description: Bcl-xL in complex with inhibitor (Compound 10)
+From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
+</div>
+<div class="pdbe-citations 4tuh" style="background-color:#fffaf0;"></div>
+==See Also==
+*[[B-cell lymphoma proteins 3D structures|B-cell lymphoma proteins 3D structures]]
+== References ==
+<references/>
+__TOC__
+</StructureSection>
+[[Category: Homo sapiens]]
+[[Category: Large Structures]]
+[[Category: Colman PM]]
+[[Category: Czabotar PE]]
+[[Category: Lessense G]]
+[[Category: Smith BJ]]

4tuh

From Proteopedia

Current revision

Bcl-xL in complex with inhibitor (Compound 10)

Structural highlights

Function

Publication Abstract from PubMed

See Also

References

Contents

Proteopedia Page Contributors and Editors (what is this?)

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