PDBsum entry 2w3l

Apoptosis

PDB id: 2w3l

Contents

Protein chain

141 a.a. *

Ligands

DRO ×2

Waters ×223

* Residue conservation analysis

PDB id:

2w3l

Name:

Apoptosis

Title:

Crystal structure of chimaeric bcl2-xl and phenyl tetrahydroisoquinoline amide complex

Structure:

Apoptosis regulator bcl-2. Chain: a, b. Fragment: residues 9-33,92-206. Synonym: bcl2-xl. Engineered: yes

Source:

Homo sapiens. Human. Organism_taxid: 9606. Expressed in: escherichia coli. Expression_system_taxid: 562

Resolution:

2.10Å R-factor: 0.218 R-free: 0.258

Authors:

J.Porter,A.Payne,B.De Candole,D.Ford,B.Hutchinson,G.Trevitt,J.Turner, C.Edwards,C.Watkins,I.Whitcombe,J.Davis,C.Stubberfield,M.Fisher, M.Lamers

Key ref:

J.Porter et al. (2009). Tetrahydroisoquinoline amide substituted phenyl pyrazoles as selective Bcl-2 inhibitors. Bioorg Med Chem Lett, 19, 230-233. PubMed id: 19027294

Date:

13-Nov-08 Release date: 09-Dec-08

Protein chains

P10415  (BCL2_HUMAN) -  Apoptosis regulator Bcl-2 from Homo sapiens

Seq: 239 a.a.

Struc: 141 a.a.*

* PDB and UniProt seqs differ at 5 residue positions (black crosses)

Enzyme reactions

• Enzyme class: E.C.?

Bioorg Med Chem Lett 19:230-233 (2009)

PubMed id: 19027294

Tetrahydroisoquinoline amide substituted phenyl pyrazoles as selective Bcl-2 inhibitors.

J.Porter, A.Payne, B.de Candole, D.Ford, B.Hutchinson, G.Trevitt, J.Turner, C.Edwards, C.Watkins, I.Whitcombe, J.Davis, C.Stubberfield.

ABSTRACT

Anti-apoptotic Bcl-2 protects cells from apoptosis by binding to pro-apoptotic members of the Bcl-2 family thereby playing a role in tumour survival in response to chemo- or radiation therapy. We describe a series of phenyl pyrazoles that have high affinity for Bcl-2 and rationalise the observed SAR by means of an X-ray crystal structure.