5c3g
From Proteopedia
Crystal structure of Bcl-xl bound to BIM-MM
Structural highlights
FunctionB2L11_HUMAN Induces apoptosis and anoikis. Isoform BimL is more potent than isoform BimEL. Isoform Bim-alpha1, isoform Bim-alpha2 and isoform Bim-alpha3 induce apoptosis, although less potent than isoform BimEL, isoform BimL and isoform BimS. Isoform Bim-gamma induces apoptosis. Isoform Bim-alpha3 induces apoptosis possibly through a caspase-mediated pathway. Isoform BimAC and isoform BimABC lack the ability to induce apoptosis.[1] [2] [3] [4] [5] [6] Publication Abstract from PubMedThe development of constrained peptides represents an emerging strategy to generate peptide based probes and hits for drug-discovery that address challenging protein-protein interactions (PPIs). In this manuscript we report on the use of a novel alpha-alkenylglycine derived amino acid to synthesise hydrocarbon constrained BH3-family sequences (BIM and BID). Our biophysical and structural analyses illustrate that whilst the introduction of the constraint increases the population of the bioactive alpha-helical conformation of the peptide in solution, it does not enhance the inhibitory potency against pro-apoptotic Bcl-xL and Mcl-1 PPIs. SPR analyses indicate binding occurs via an induced fit mechanism whilst X-ray analyses illustrate none of the key interactions between the helix and protein are disturbed. The behaviour derives from enthalpy-entropy compensation which may be considered in terms of the ground state energies of the unbound constrained and unconstrained peptides; this has implications for the design of preorganised peptides to target protein-protein interactions. Hydrocarbon constrained peptides - understanding preorganisation and binding affinity.,Miles JA, Yeo DJ, Rowell P, Rodriguez-Marin S, Pask CM, Warriner SL, Edwards TA, Wilson AJ Chem Sci. 2016 Jun 1;7(6):3694-3702. doi: 10.1039/c5sc04048e. Epub 2016 Feb 29. PMID:28970875[7] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See AlsoReferences
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Categories: Homo sapiens | Large Structures | Mus musculus | Edwards TA | Miles JA | Pask CM | Rodriguez-Marin S | Rowell P | Warriner SL | Wilson AJ | Yeo DJ
