4aq3

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4aq3, resolution 2.40Å ()
Ligands:
Related: 1bxl, 1g5j, 1g5m, 1gjh, 1lxl, 1maz, 1r2d, 1r2e, 1r2g, 1r2h, 1r2i, 1ysg, 1ysi, 1ysn, 1ysw, 2b48, 2w3l, 2xa0, 2yj1, 4a1u, 4a1w


Resources: FirstGlance, OCA, RCSB, PDBsum
Coordinates: save as pdb, mmCIF, xml


Contents

HUMAN BCL-2 WITH PHENYLACYLSULFONAMIDE INHIBITOR

Publication Abstract from PubMed

A series of phenylacylsulfonamides has been prepared as antagonists of Bcl-2/Bcl-xL. In addition to potent binding affinities for both Bcl-2 and Bcl-xL, these compounds were shown to induce classical markers of apoptosis in isolated mitochondria. Overall weak cellular potency was improved by the incorporation of polar functionality resulting in compounds with moderate antiproliferative activity.

Identification of a phenylacylsulfonamide series of dual Bcl-2/Bcl-xL antagonists., Perez HL, Banfi P, Bertrand J, Cai ZW, Grebinski JW, Kim K, Lippy J, Modugno M, Naglich J, Schmidt RJ, Tebben A, Vianello P, Wei DD, Zhang L, Galvani A, Lombardo LJ, Borzilleri RM, Bioorg Med Chem Lett. 2012 Jun 15;22(12):3946-50. Epub 2012 May 2. PMID:22608961

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

Disease

[BCL2_HUMAN] Note=A chromosomal aberration involving BCL2 has been found in chronic lymphatic leukemia. Translocation t(14;18)(q32;q21) with immunoglobulin gene regions. BCL2 mutations found in non-Hodgkin lymphomas carrying the chromosomal translocation could be attributed to the Ig somatic hypermutation mechanism resulting in nucleotide transitions.

Function

[BCL2_HUMAN] Suppresses apoptosis in a variety of cell systems including factor-dependent lymphohematopoietic and neural cells. Regulates cell death by controlling the mitochondrial membrane permeability. Appears to function in a feedback loop system with caspases. Inhibits caspase activity either by preventing the release of cytochrome c from the mitochondria and/or by binding to the apoptosis-activating factor (APAF-1).[1]

About this Structure

4aq3 is a 6 chain structure with sequence from Homo sapiens. Full crystallographic information is available from OCA.

Reference

  • Perez HL, Banfi P, Bertrand J, Cai ZW, Grebinski JW, Kim K, Lippy J, Modugno M, Naglich J, Schmidt RJ, Tebben A, Vianello P, Wei DD, Zhang L, Galvani A, Lombardo LJ, Borzilleri RM. Identification of a phenylacylsulfonamide series of dual Bcl-2/Bcl-xL antagonists. Bioorg Med Chem Lett. 2012 Jun 15;22(12):3946-50. Epub 2012 May 2. PMID:22608961 doi:10.1016/j.bmcl.2012.04.103
  1. Wei Y, Pattingre S, Sinha S, Bassik M, Levine B. JNK1-mediated phosphorylation of Bcl-2 regulates starvation-induced autophagy. Mol Cell. 2008 Jun 20;30(6):678-88. doi: 10.1016/j.molcel.2008.06.001. PMID:18570871 doi:10.1016/j.molcel.2008.06.001

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