4J48

Crystal structure of XIAP-BIR2 domain with AMRV bound

Summary for 4J48

• Entry DOI: 10.2210/pdb4j48/pdb
• Related: 1I3O 4J3Y 4J44 4J45 4J46 4J47
• Descriptor: E3 ubiquitin-protein ligase XIAP, PEPTIDE (ALA-MET-ARG-VAL), ZINC ION, ... (6 entities in total)
• Functional Keywords: iap, xiap, caspase, apoptosis, smac
• Biological source: Homo sapiens (human); More
• Cellular location: Cytoplasm: P98170
• Total number of polymer chains: 3
• Total formula weight: 20667.85

Authors

Gosu, R. (deposition date: 2013-02-06, release date: 2013-09-25, Last modification date: 2023-09-20)

Primary citation

Lukacs, C.,Belunis, C.,Crowther, R.,Danho, W.,Gao, L.,Goggin, B.,Janson, C.A.,Li, S.,Remiszewski, S.,Schutt, A.,Thakur, M.K.,Singh, S.K.,Swaminathan, S.,Pandey, R.,Tyagi, R.,Gosu, R.,Kamath, A.V.,Kuglstatter, A.
The structure of XIAP BIR2: understanding the selectivity of the BIR domains.
Acta Crystallogr.,Sect.D, 69:1717-1725, 2013

PubMed Abstract: XIAP, a member of the inhibitor of apoptosis family of proteins, is a critical regulator of apoptosis. Inhibition of the BIR domain-caspase interaction is a promising approach towards treating cancer. Previous work has been directed towards inhibiting the BIR3-caspase-9 interaction, which blocks the intrinsic apoptotic pathway; selectively inhibiting the BIR2-caspase-3 interaction would also block the extrinsic pathway. The BIR2 domain of XIAP has successfully been crystallized; peptides and small-molecule inhibitors can be soaked into these crystals, which diffract to high resolution. Here, the BIR2 apo crystal structure and the structures of five BIR2-tetrapeptide complexes are described. The structural flexibility observed on comparing these structures, along with a comparison with XIAP BIR3, affords an understanding of the structural elements that drive selectivity between BIR2 and BIR3 and which can be used to design BIR2-selective inhibitors.

PubMed: 23999295
DOI: 10.1107/S0907444913016284

Experimental method

X-RAY DIFFRACTION (2.1 Å)