3EYL

Crystal structure of XIAP BIR3 domain in complex with a Smac-mimetic compound

Summary for 3EYL

• Entry DOI: 10.2210/pdb3eyl/pdb
• Related: 1g73 3clx 3cm2 3cm7
• Descriptor: Baculoviral IAP repeat-containing protein 4, ZINC ION, (3S,6S,7R,9aS)-6-{[(2S)-2-aminobutanoyl]amino}-7-(2-aminoethyl)-N-(diphenylmethyl)-5-oxooctahydro-1H-pyrrolo[1,2-a]azepine-3-carboxamide, ... (4 entities in total)
• Functional Keywords: apoptosis, smac-mimetics, zinc-finger, ligase, metal-binding, phosphoprotein, protease inhibitor, thiol protease inhibitor, ubl conjugation pathway
• Biological source: Homo sapiens (human)
• Cellular location: Cytoplasm: P98170
• Total number of polymer chains: 2
• Total formula weight: 29387.40

Authors

Cossu, F.,Milani, M.,Mastrangelo, E.,Bolognesi, M. (deposition date: 2008-10-21, release date: 2008-11-25, Last modification date: 2023-09-06)

Primary citation

Cossu, F.,Mastrangelo, E.,Milani, M.,Sorrentino, G.,Lecis, D.,Delia, D.,Manzoni, L.,Seneci, P.,Scolastico, C.,Bolognesi, M.
Designing Smac-mimetics as antagonists of XIAP, cIAP1, and cIAP2.
Biochem.Biophys.Res.Commun., 378:162-167, 2009

PubMed Abstract: Inhibitor of apoptosis proteins (IAPs) such as XIAP, cIAP1, and cIAP2 are upregulated in many cancer cells. Several compounds targeting IAPs and inducing cell death in cancer cells have been developed. Some of these are synthesized mimicking the N-terminal tetrapeptide sequence of Smac/DIABLO, the natural endogenous IAPs inhibitor. Starting from such conceptual design, we generated a library of 4-substituted azabicyclo[5.3.0]alkane Smac-mimetics. Here we report the crystal structure of the BIR3 domain from XIAP in complex with Smac037, a compound designed according to structural principles emerging from our previously analyzed XIAP BIR3/Smac-mimetic complexes. In parallel, we present an in silico docking analysis of three Smac-mimetics to the BIR3 domain of cIAP1, providing general considerations for the development of high affinity lead compounds targeting three members of the IAP family.

PubMed: 18992220
DOI: 10.1016/j.bbrc.2008.10.139

Experimental method

X-RAY DIFFRACTION (3 Å)