4J47

Crystal structure of XIAP-BIR2 domain with SVPI bound

4J47 の概要

• エントリーDOI: 10.2210/pdb4j47/pdb
• 関連するPDBエントリー: 1I3O 4J3Y 4j44 4j45 4j46
• 分子名称: E3 ubiquitin-protein ligase XIAP, PEPTIDE (SER-VAL-PRO-ILE), ZINC ION, ... (4 entities in total)
• 機能のキーワード: iap, xiap, caspase, apoptosis, smac, apoptosis inhibitor
• 由来する生物種: Homo sapiens (human); 詳細
• タンパク質・核酸の鎖数: 3
• 化学式量合計: 20417.58

構造登録者

Lukacs, C.M.,Janson, C.A. (登録日: 2013-02-06, 公開日: 2013-09-25, 最終更新日: 2023-09-20)

主引用文献

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

実験手法

X-RAY DIFFRACTION (1.35 Å)