Many cancers overexpress one or more of the six human pro-survival BCL2 family proteins to evade apoptosis. To determine which BCL2 protein or proteins block apoptosis in different cancers, we computationally designed three-helix bundle protein inhibitors specific for each BCL2 pro-survival protein. Following in vitro optimization, each inhibitor binds its target with high picomolar to low nanomolar affinity and at least 300-fold specificity. Expression of the designed inhibitors in human cancer cell lines revealed unique dependencies on BCL2 proteins for survival which could not be inferred from other BCL2 profiling methods. Our results show that designed inhibitors can be generated for each member of a closely-knit protein family to probe the importance of specific protein-protein interactions in complex biological processes.
Pubmed ID: 27805565 RIS Download
Publication data is provided by the National Library of Medicine ® and PubMed ®. Data is retrieved from PubMed ® on a weekly schedule. For terms and conditions see the National Library of Medicine Terms and Conditions.
Global nonprofit biological resource center (BRC) and research organization that provides biological products, technical services and educational programs to private industry, government and academic organizations. Its mission is to acquire, authenticate, preserve, develop and distribute biological materials, information, technology, intellectual property and standards for the advancement and application of scientific knowledge. The primary purpose of ATCC is to use its resources and experience as a BRC to become the world leader in standard biological reference materials management, intellectual property resource management and translational research as applied to biomaterial development, standardization and certification. ATCC characterizes cell lines, bacteria, viruses, fungi and protozoa, as well as develops and evaluates assays and techniques for validating research resources and preserving and distributing biological materials to the public and private sector research communities.
View all literature mentionsMolecular modeling software package for 3D structure prediction and high resolution design of proteins, nucleic acids, and non natural polymers. Used in computational biology, including de novo protein design, enzyme design, ligand docking, and structure prediction of biological macromolecules and macromolecular complexes.
View all literature mentionsMus musculus with name C57BL/6J from IMSR.
View all literature mentionsThis monoclonal targets Bcl-2 (C-2)
View all literature mentionsThis monoclonal targets α-Tubulin
View all literature mentionsThis monoclonal targets FLAG??
View all literature mentionsThis monoclonal targets Cytochrome c
View all literature mentionsThis monoclonal targets HA
View all literature mentionsThis polyclonal targets MCL1 antibody
View all literature mentionsThis polyclonal targets BCL2L1
View all literature mentionsThis monoclonal targets β-Actin
View all literature mentionsThis unknown targets Mouse Mcl-1
View all literature mentionsThis polyclonal targets FLAG
View all literature mentionsTHIS RESOURCE IS NO LONGER IN SERVICE, documented on July 16, 2013. Following completion of the acquisition of Rosetta Biosoftware assets from Merck & Co., Inc. by Microsoft Corp. on June 26, 2009, Merck & Co., Inc. selected Ceiba Solutions, Inc (http://www.ceibasolutions.com) as the provider of product support for Rosetta Resolver, Elucidator and Syllego customers. Ceiba Solutions is a software and IT services company helping customers streamline and extend business processes through composite software development, application integration, and managed application services. Ceiba currently serves Life Science industry customers with outsourced managed services for R&D applications, as well as business software and integrated business processes. Ceiba Solutions is an active member of the Massachusetts Biotechnology Council and the BayBio Council. Ceiba Solutions has assumed complete responsibility for software maintenance and support associated with Rosetta Biosoftware product Licensees who are eligible for continued Technical Support and Software Upgrade Protection, and will retain that responsibility throughout the remainder of the 24 month Desupport Period.
View all literature mentionsCell line HEK293T is a Transformed cell line with a species of origin Homo sapiens (Human)
View all literature mentionsSoftware for macromolecular model building, model completion and validation, and protein modelling using X-ray data. Coot displays maps and models and allows model manipulations such as idealization, rigid-body fitting, ligand search, Ramachandran plots, non-crystallographic symmetry and more. Source code is available.
View all literature mentionsPortal for Macromolecular X-Ray Crystallography to produce and support an integrated suite of programs that allows researchers to determine macromolecular structures by X-ray crystallography, and other biophysical techniques. Used in the education and training of scientists in experimental structural biology for determination and analysis of protein structure.
View all literature mentionsCrystallographic software which solves structures using algorithms and automated rapid search calculations to perform molecular replacement and experimental phasing methods.
View all literature mentionsA molecular refinement program with two main modes: REVIEW, which checks and updates the input model to establish that the geometric restraints can be properly set up, and REFINE mode, which is the standard mode and documented in keywords. In REVIEW users can: check model coordinates and write an extended output set of coordinates, find disulphide bonds and other covalent links, cis-peptides, output the sequence and REMARK records. In REFINEMENT mode users can carry out rigid body, tls, restrained or unrestrained refinement against Xray data, or idealisation of a macromolecular structure. Also in REFINEMENT mode, Refmac produces an MTZ output file containing weighted coefficients for SigmaA weighted mFo-DFcalc and 2mFo-DFcalc maps. The program is supported by CCP4.
View all literature mentionsCell line SW48 is a Cancer cell line with a species of origin Homo sapiens (Human)
View all literature mentionsCell line Caco-2 is a Cancer cell line with a species of origin Homo sapiens (Human)
View all literature mentionsCell line HT-29 is a Cancer cell line with a species of origin Homo sapiens (Human)
View all literature mentionsCell line RKO is a Cancer cell line with a species of origin Homo sapiens (Human)
View all literature mentionsCell line DLD-1 is a Cancer cell line with a species of origin Homo sapiens (Human)
View all literature mentionsCell line HCT 116 is a Cancer cell line with a species of origin Homo sapiens (Human)
View all literature mentionsCell line SW620 is a Cancer cell line with a species of origin Homo sapiens (Human)
View all literature mentionsCell line U-87MG ATCC is a Cancer cell line with a species of origin Homo sapiens (Human)
View all literature mentionsCell line LOX-IMVI is a Cancer cell line with a species of origin Homo sapiens (Human)
View all literature mentionsCell line SK-MEL-5 is a Cancer cell line with a species of origin Homo sapiens (Human)
View all literature mentionsCell line HeLa is a Cancer cell line with a species of origin Homo sapiens
View all literature mentions