Cdk2 allosteric pocket
WebCyclin-dependent kinase 2 (CDK2) is part of the larger CDK family of kinases that regulate the mitotic cell cycle. It is activated by the binding of E-type cyclins at the G1-S transition … WebBinding of ANS is accompanied by substantial structural changes in CDK2, resulting in a C-helix conformation that is incompatible for cyclin A association. These findings indicate …
Cdk2 allosteric pocket
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WebJan 5, 2024 · In a recently identified inactive conformation of cyclin-dependent kinase 2 (CDK2), an open allosteric pocket was detected and proposed as a site to … WebApr 20, 2012 · The assay is based on the specific interaction of CDK2 with the extrinsic fluorophore 8-anilino-1-naphthalene sulfonate (ANS), which binds to a large allosteric pocket adjacent to the ATP site. Hit compounds that displace ANS directly or indirectly from CDK2 are readily classified as ATP site binders or allosteric ligands through the use of ...
WebJan 5, 2024 · The availability of well‐characterized allosteric modulators is crucial for investigating the allosteric regulation of protein function. In a recently identified inactive conformation of cyclin‐dependent kinase 2 (CDK2), an open allosteric pocket was detected and proposed as a site to accommodate allosteric inhibitors. Previous … WebRecently, the first crystal structure of CDK2 with an open allosteric pocket adjacent to the αC helix has been described, prospecting new opportunities to design more selective inhibitors, but the structure has not yet been exploited for the structure-based design of type III allosteric inhibitors. In this work we report the results of a ...
WebThe availability of well-characterized allosteric modulators is crucial for investigating the allosteric regulation of protein function. In a recently identified inactive conformation of cyclin-dependent kinase 2 (CDK2), … WebDespite the status of cyclin-dependent kinase 2 (CDK2) as a validated target for both anticancer and contraceptive indications, a CDK2 inhibitor with exquisite selectivity has …
WebAllosteric targeting of protein kinases via displacement of the structural αC helix with type III allosteric inhibitors is currently gaining a foothold in drug discovery. Recently, the first crystal structure of CDK2 with an open allosteric pocket adjacent to the αC helix has been described, prospec …
WebNov 10, 2024 · Recently, a novel allosteric pocket on CDK2 was uncovered and it was quickly translated into the development of a set of allosteric inhibitors for the CDK2–cyclin A3 PPI (Fig. 13.1). In the research carried out by Hu et al., virtual screening is combined with bioassays to yield the promising lead compounds. meritage wine storeWebJan 1, 2024 · These programs have developed compounds that bind tightly to cyclin-free CDK2 by exploiting an allosteric pocket and, in one case (Alexander et al., 2015), ... Willis A., Noble M.E., Endicott J.A. How tyrosine 15 phosphorylation inhibits the activity of cyclin-dependent kinase 2-cyclin A. J. Biol. Chem. 2007; 282:3173–3181. [Google ... merit aid by institutionWebJul 2, 2024 · Compared to most ATP-site kinase inhibitors, small molecules that target an allosteric pocket have the potential for improved selectivity due to the often observed lower structural similarity at these distal sites. Despite their promise, relatively few examples of structurally confirmed, high-affinity allosteric kinase inhibitors exist. Cyclin-dependent … merit aid college transitionsWebWe previously discovered an allosteric pocket in CDK2 with potential to bind a compound with desirable selectivity. Using high-throughput and virtual screening methods, we discovered and structurally confirmed an anthranilic acid scaffold that binds this pocket with high affinity. We previously reported that these allosteric CDK2 inhibitors ... how old was tori in victoriousWebJan 18, 2024 · Born in 1965, Katherine Gray attended the Rhode Island School of Design and the Ontario College of Art, in Toronto, Canada. A huge proponent of handiwork and … meritage villages of minneolaWebAlthough cyclin-dependent kinase 2 (CDK2) is a validated target for both cancer and contraception, developing a CDK2 inhibitor with exquisite selectivity has been … merit aid boston collegeWebJan 10, 2024 · The inside cover picture shows the first small-molecule allosteric inhibitor of cyclin-dependent kinase 2 (CDK2) binding within an allosteric pocket in the proximity of the αC helix and distinct from the ATP binding site. The target compound was fully characterized through chemical synthesis, X-ray crystallography, modeling studies, and … how old was toph beifong in atla