3OZ1

cIAP1-BIR3 domain in complex with the Smac-mimetic compound Smac066

Summary for 3OZ1

• Entry DOI: 10.2210/pdb3oz1/pdb
• Related: 3MUP
• Descriptor: Baculoviral IAP repeat-containing protein 2, ZINC ION, (3S,6S,7R,9aS)-7-[2-(benzylamino)ethyl]-N-(diphenylmethyl)-6-{[(2S)-2-(methylamino)butanoyl]amino}-5-oxooctahydro-1H-pyrrolo[1,2-a]azepine-3-carboxamide, ... (4 entities in total)
• Functional Keywords: zinc-finger, caspases, apoptosis inhibitor
• Biological source: Homo sapiens (human)
• Cellular location: Cytoplasm (Potential): Q13490
• Total number of polymer chains: 4
• Total formula weight: 60261.80

Authors

Cossu, F.,Malvezzi, F.,Mastrangelo, E.,Canevari, G.,Bolognesi, M.,Milani, M. (deposition date: 2010-09-24, release date: 2010-11-24, Last modification date: 2024-03-20)

Primary citation

Cossu, F.,Malvezzi, F.,Canevari, G.,Mastrangelo, E.,Lecis, D.,Delia, D.,Seneci, P.,Scolastico, C.,Bolognesi, M.,Milani, M.
Recognition of Smac-mimetic compounds by the BIR3 domain of cIAP1
Protein Sci., 2010

PubMed Abstract: Inhibitor of apoptosis proteins (IAPs) are negative regulators of apoptosis. As IAPs are overexpressed in many tumors, where they confer chemoresistance, small molecules inactivating IAPs have been proposed as anticancer agents. Accordingly, a number of IAP-binding pro-apoptotic compounds that mimic the sequence corresponding to the N-terminal tetrapeptide of Smac/DIABLO, the natural endogenous IAPs inhibitor, have been developed. Here, we report the crystal structures of the BIR3 domain of cIAP1 in complex with Smac037, a Smac-mimetic known to bind potently to the XIAP-BIR3 domain and to induce degradation of cIAP1, and in complex with the novel Smac-mimetic compound Smac066. Thermal stability and fluorescence polarization assays show the stabilizing effect and the high affinity of both Smac037 and Smac066 for cIAP1- and cIAP2-BIR3 domains.

PubMed: 20954235
DOI: 10.1002/pro.523

Experimental method

X-RAY DIFFRACTION (3 Å)