2JK7

XIAP BIR3 bound to a Smac Mimetic

Summary for 2JK7

• Entry DOI: 10.2210/pdb2jk7/pdb
• Related: 1C9Q 1F9X 1G3F 1G73 1I3O 1I4O 1I51 1KMC 1NW9 1TFQ 1TFT 2VSL
• Descriptor: BACULOVIRAL IAP REPEAT-CONTAINING PROTEIN 4, (3S,6S,7Z,10AS)-N-(DIPHENYLMETHYL)-6-{[(2S)-2-(METHYLIDENEAMINO)BUTANOYL]AMINO}-5-OXO-1,2,3,5,6,9,10,10A-OCTAHYDROPYRROLO[1,2-A]AZOCINE-3-CARBOXAMIDE, ZINC ION, ... (4 entities in total)
• Functional Keywords: zinc-finger, polymorphism, smac mimetic, metal-binding, bir3, zinc, ligase, apoptosis, cytoplasm, x-linked inhibitor of apoptosis, ubl conjugation pathway, thiol protease inhibitor, phosphoprotein, ubl conjugation, protease inhibitor
• Biological source: HOMO SAPIENS (HUMAN)
• Cellular location: Cytoplasm: P98170
• Total number of polymer chains: 1
• Total formula weight: 13845.77

Authors

Saito, N.G.,Meagher, J.L.,Stuckey, J.A. (deposition date: 2008-08-21, release date: 2008-11-04, Last modification date: 2024-05-01)

Primary citation

Sun, H.,Stuckey, J.A.,Nikolovska-Coleska, Z.,Qin, D.,Meagher, J.L.,Qiu, S.,Lu, J.,Yang, C.,Saito, N.G.,Wang, S.
Structure-Based Design, Synthesis, Evaluation, and Crystallographic Studies of Conformationally Constrained Smac Mimetics as Inhibitors of the X-Linked Inhibitor of Apoptosis Protein (Xiap).
J.Med.Chem., 51:7169-, 2008

PubMed Abstract: Small molecules designed to mimic the binding of Smac protein to X-linked inhibitor of apoptosis protein (XIAP) are being pursued as a promising new class of anticancer drugs. Herein, we report the design, synthesis, and comprehensive structure-activity relationship studies of a series of conformationally constrained bicyclic Smac mimetics. Our studies led to the discovery of a number of highly potent and cell-permeable Smac mimetics and yielded important new insights into their structure-activity relationship for their binding to XIAP and for their activity in inhibition of cancer cell growth. Determination of the crystal structure of one potent Smac mimetic, compound 21, in complex with XIAP BIR3 provides the structural basis for its high-affinity binding to XIAP and for the design of highly potent Smac mimetics.

PubMed: 18954041
DOI: 10.1021/JM8006849

Experimental method

X-RAY DIFFRACTION (2.82 Å)