4g35

Mcl-1 in complex with a biphenyl cross-linked Noxa peptide.

spinqualitylabelsall models 4g35, resolution 2.00Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 4g35 is a 2 chain structure with sequence from Mus musculus. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance. Method: X-ray diffraction, Resolution 2Å Ligands: 4BP, ACE, DCY, NH2 Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT Function MCL1_MOUSE Involved in the regulation of apoptosis versus cell survival, and in the maintenance of viability but not of proliferation. Mediates its effects by interactions with a number of other regulators of apoptosis. Publication Abstract from PubMed Direct chemical modifications provide a simple and effective means to "translate" bioactive helical peptides into potential therapeutics targeting intracellular protein-protein interactions. We previously showed that distance-matching bisaryl cross-linkers can reinforce peptide helices containing two cysteines at the i and i+7 positions and confer cell permeability to the cross-linked peptides. Here we report the first crystal structure of a biphenyl-cross-linked Noxa peptide in complex with its target Mcl-1 at 2.0 A resolution. Guided by this structure, we remodeled the surface of this cross-linked peptide through side-chain substitution and N-methylation and obtained a pair of cross-linked peptides with substantially increased helicity, cell permeability, proteolytic stability, and cell-killing activity in Mcl-1-overexpressing U937 cells. Rational design of proteolytically stable, cell-permeable peptide-based selective Mcl-1 inhibitors.,Muppidi A, Doi K, Edwardraja S, Drake EJ, Gulick AM, Wang HG, Lin Q J Am Chem Soc. 2012 Sep 12;134(36):14734-7. doi: 10.1021/ja306864v. Epub 2012 Sep, 4. PMID:22920569 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See Also B-cell lymphoma proteins 3D structures

Proteopedia Page Contributors and Editors (what is this?)

OCA