4a1w

Crystal structure of alpha-beta foldamer 4c in complex with Bcl-xL

spinqualitylabelsall models 4a1w, resolution 2.50Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 4a1w is a 8 chain structure with sequence from Human. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance. NonStd Res: 3FB, B3E, B3Y, BIL, HT7, NH2 Related: 4a1u Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT Function [B2CL1_HUMAN] Potent inhibitor of cell death. Inhibits activation of caspases (By similarity). Appears to regulate cell death by blocking the voltage-dependent anion channel (VDAC) by binding to it and preventing the release of the caspase activator, CYC1, from the mitochondrial membrane. Also acts as a regulator of G2 checkpoint and progression to cytokinesis during mitosis. Isoform Bcl-X(S) promotes apoptosis. Publication Abstract from PubMed Peptidic oligomers that contain both alpha- and beta-amino acid residues, in regular patterns throughout the backbone, are emerging as structural mimics of alpha-helix-forming conventional peptides (composed exclusively of alpha-amino acid residues). Here we describe a comprehensive evaluation of diverse alpha/beta-peptide homologues of the Bim BH3 domain in terms of their ability to bind to the BH3-recognition sites on two partner proteins, Bcl-x(L) and Mcl-1. These proteins are members of the anti-apoptotic Bcl-2 family, and both bind tightly to the Bim BH3 domain itself. All alpha/beta-peptide homologues retain the side-chain sequence of the Bim BH3 domain, but each homologue contains periodic alpha-residue --> beta(3)-residue substitutions. Previous work has shown that the alphaalphabetaalphaalphaalphabeta pattern, which aligns the beta(3)-residues in a 'stripe' along one side of the helix, can support functional alpha-helix mimicry, and the results reported here strengthen this conclusion. The present study provides the first evaluation of functional mimicry by alphaalphabeta and alphaalphaalphabeta patterns, which cause the beta(3)-residues to spiral around the helix periphery. We find that the alphaalphaalphabeta pattern can support effective mimicry of the Bim BH3 domain, as manifested by the crystal structure of an alpha/beta-peptide bound to Bcl-x(L), affinity for a variety of Bcl-2 family proteins, and induction of apoptotic signaling in mouse embryonic fibroblast extracts. The best alphaalphaalphabeta homologue shows substantial protection from proteolytic degradation relative to the Bim BH3 alpha-peptide. Evaluation of Diverse alpha/beta-Backbone Patterns for Functional alpha-Helix Mimicry: Analogues of the Bim BH3 Domain.,Boersma MD, Haase HS, Peterson-Kaufman KJ, Lee EF, Clarke OB, Colman PM, Smith BJ, Horne WS, Fairlie WD, Gellman SH J Am Chem Soc. 2011 Dec 8. PMID:22040025 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See Also B-cell lymphoma protein

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