Design and synthesis of a simplified inhibitor for XIAP-BIR3 domain

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Designing a new tetrapeptide to inhibit the BIR3 domain of the XIAP protein via molecular dynamics simulations

The XIAP protein is a member of apoptosis proteins family. The XIAP protein plays a central role in the inhibition of apoptosis and consists of three Baculoviral IAP Repeat domains. The BIR3 domain binds directly to the N-terminal of caspase-9 and therefore it inhibits apoptosis. N-terminal tetrapeptide region of SMAC protein can bind to BIR3, inhibit it and subsequently induce apoptosis. In th...

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NMR structure and mutagenesis of the third Bir domain of the inhibitor of apoptosis protein XIAP.

The inhibitor of apoptosis proteins (IAPs) regulate the caspase family of cysteine proteases, which play an important role in the execution of programmed cell death. Human X-linked inhibitor of apoptosis protein (XIAP) is a potent inhibitor of caspases-3, -7, and -9. Here we show that the Bir3 domain is the minimal region of XIAP that is needed for potent caspase-9 inhibition. The three-dimensi...

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ژورنال

عنوان ژورنال: Bioorganic & Medicinal Chemistry Letters

سال: 2009

ISSN: 0960-894X

DOI: 10.1016/j.bmcl.2009.09.058