Related ArticlesNMR-Derived Conformational Ensemble of State 1 of Activated Ras Reveals Insights into a Druggable Pocket.
J Phys Chem Lett. 2020 Apr 17;:
Authors: Liu D, Chen X, Long D
Abstract
Lack of apparent pockets in the ground conformation of Ras has long challenged the rational design of inhibitors against this oncogenic protein. The sparsely populated, transiently formed state 1 of activated Ras, on the other hand, shows appreciable surface roughness and is increasingly recognized as a potential target for drug discovery. The state 1, however, is extremely flexible, and a static structure cannot fully unveil its conformational space that can be exploited for drug design. Here, we present a conformational ensemble of state 1 that was derived using chemical shift-based modelling. The ensemble reveals the intrinsic plasticity of a druggable pocket in state 1 and demonstrates the mechanism of conformational selection for inhibitor recognition. The large set of structural templates in the ensemble, providing a comprehensive description of thermally accessible pocket conformations, are expected to significantly aid the rational design of anti-Ras drugs.
PMID: 32302142 [PubMed - as supplied by publisher]
When Heterotrimeric G Proteins Are Not Activated by G Protein-Coupled Receptors: Structural Insights and Evolutionary Conservation
When Heterotrimeric G Proteins Are Not Activated by G Protein-Coupled Receptors: Structural Insights and Evolutionary Conservation
http://pubs.acs.org/appl/literatum/publisher/achs/journals/content/bichaw/0/bichaw.ahead-of-print/acs.biochem.7b00845/20171016/images/medium/bi-2017-00845a_0003.gif
Biochemistry
DOI: 10.1021/acs.biochem.7b00845
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[NMR paper] The Influenza M2 Ectodomain Regulates the Conformational Equilibria of the Transmembrane Proton Channel: Insights from Solid-State NMR.
The Influenza M2 Ectodomain Regulates the Conformational Equilibria of the Transmembrane Proton Channel: Insights from Solid-State NMR.
http://www.bionmr.com//www.ncbi.nlm.nih.gov/corehtml/query/egifs/http:--pubs.acs.org-images-pubmed-acspubs.jpg Related Articles The Influenza M2 Ectodomain Regulates the Conformational Equilibria of the Transmembrane Proton Channel: Insights from Solid-State NMR.
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Authors: Kwon B, Hong M
Abstract
The influenza M2 protein is the target of the amantadine family of...
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[NMR paper] A Conformational Ensemble Derived Using NMR Methyl Chemical Shifts Reveals a Mechanical Clamping Transition That Gates the Binding of the HU Protein to DNA.
A Conformational Ensemble Derived Using NMR Methyl Chemical Shifts Reveals a Mechanical Clamping Transition That Gates the Binding of the HU Protein to DNA.
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J Am Chem Soc. 2014 Feb 12;136(6):2204-7
Authors: Kannan A, Camilloni C, Sahakyan AB, Cavalli A, Vendruscolo M
Abstract
Recent improvements in the accuracy of structure-based methods for the prediction of...
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[NMR paper] NMR reveals the allosteric opening and closing of Abelson tyrosine kinase by ATP-site and myristoyl pocket inhibitors.
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Proc Natl Acad Sci U S A. 2013 Nov 4;
Authors: Skora L, Mestan J, Fabbro D, Jahnke W, Grzesiek S
Abstract
Successful treatment of chronic myelogenous leukemia is based on inhibitors binding to the ATP site of the deregulated breakpoint cluster region (Bcr)-Abelson tyrosine kinase (Abl)...
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CoNSEnsX: an ensemble view of protein structures and NMR-derived experimental data.
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BMC Struct Biol. 2010 Oct 29;10(1):39
Authors: Angyan AF, Szappanos B, Perczel A, Gaspari Z
ABSTRACT: BACKGROUND: In conjunction with the recognition of the functional role of internal dynamics of proteins at various timescales, there is an emerging use of dynamic structural ensembles instead of individual conformers. These ensembles are usually substantially...
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CoNSEnsX: an ensemble view of protein structures and NMR-derived experimental data -
CoNSEnsX: an ensemble view of protein structures and NMR-derived experimental data - 7thSpace Interactive (press release)
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CoNSEnsX: an ensemble view of protein structures and NMR-derived experimental data
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These ensembles are usually substantially more diverse than conventional NMR ensembles and eliminate the expectation that a single conformer should fulfill ...
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[NMR paper] An automated approach for clustering an ensemble of NMR-derived protein structures in
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Authors: Kelley LA, Gardner SP, Sutcliffe MJ
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[NMR paper] Representing an ensemble of NMR-derived protein structures by a single structure.
Representing an ensemble of NMR-derived protein structures by a single structure.
http://www.ncbi.nlm.nih.gov/corehtml/query/egifs/http:--www3.interscience.wiley.com-aboutus-images-wiley_interscience_pubmed_logo_FREE_120x27.gif http://www.ncbi.nlm.nih.gov/corehtml/query/egifs/http:--www.pubmedcentral.nih.gov-corehtml-pmc-pmcgifs-pubmed-pmc.gif Related Articles Representing an ensemble of NMR-derived protein structures by a single structure.
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NMR-Derived Conformational Ensemble of State 1 of Activated Ras Reveals Insights into a Druggable Pocket.
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