We describe a refined homology model of a CDK1/cyclin B complex that was previously used for the structure-based optimization of the Paullone class of inhibitors. The preliminary model was formed from the homologous regions of the deposited CDK2/cyclin A crystal structure. Further refinement of the CDK1/cyclin B complex was accomplished using molecular mechanics and hydropathic analysis with a protocol of constraints and local geometry searches. For the most part, our CKD1/cyclin B homology model is very similar to the high resolution CDK2/cyclin A crystal structure regarding secondary and tertiary features. However, minor discrepancies between the two kinase structures suggest the possibility that ligand design may be specifically tuned for either CDK1 or CDK2. Our examination of the CDK1/cyclin B model includes a comparison with the CDK2/cyclin A crystal structure in the PSTAIRE interface region, connecting portions to the ATP binding domain, as well as the ATP binding site itself.
Download full-text PDF |
Source |
|---|---|
| http://dx.doi.org/10.1080/07391102.2005.10531227 | DOI Listing |
Publication Analysis
Top Keywords
Similar Publications
Background: Christianson syndrome (CS) is an x-linked recessive neurodevelopmental and neurodegenerative condition characterized by severe intellectual disability, cerebellar degeneration, ataxia, and epilepsy. Mutations to the gene encoding NHE6 are responsible for CS, and we recently demonstrated that a mutation to the rat gene causes a similar phenotype in the spontaneous rat model, which exhibits cerebellar degeneration with motor dysfunction. In previous work, we used the PhP.
View Article and Find Full Text PDFComputational identification of novel natural inhibitors against triple mutant DNA gyrase A in fluoroquinolone-resistant Typhimurium.
Biochem Biophys Rep
March 2025
Department of Integrative Biology, School of Biosciences and Technology, Vellore Institute of Technology (VIT), Vellore, 632014, Tamil Nadu, India.
The rising resistance to fluoroquinolones in Typhimurium poses a significant global health challenge. This computational research addresses the pressing need for new therapeutic drugs by utilizing various computational tools to identify potential natural compounds that can inhibit the triple mutant DNA gyrase subunit A enzyme, which is crucial in fluoroquinolone resistance. Initially, the three-dimensional structure of the wild-type DNA gyrase A protein was modeled using homology modeling, and followed by mutagenesis to create the clinically relevant triple mutant (SER83PHE, ASP87GLY, ALA119SER) DNA gyrase A protein structure.
View Article and Find Full Text PDFWho is WithMe? EEG features for attention in a visual task, with auditory and rhythmic support.
Front Neurosci
January 2025
Department of Mathematics, University of Antwerp-Interuniversity Microelectronics Centre (imec), Antwerp, Belgium.
Introduction: The study of attention has been pivotal in advancing our comprehension of cognition. The goal of this study is to investigate which EEG data representations or features are most closely linked to attention, and to what extent they can handle the cross-subject variability.
Methods: We explore the features obtained from the univariate time series from a single EEG channel, such as time domain features and recurrence plots, as well as representations obtained directly from the multivariate time series, such as global field power or functional brain networks.
Metacaspases-Like Proteases of Trichomonas vaginalis: In Silico Identification and Characterization.
J Basic Microbiol
January 2025
Laboratorio de Bioquímica y Genética Molecular, Facultad de Química, Universidad Autónoma de Yucatán, Mérida, Yucatán, México.
Metacaspases (MCA), are cysteine-dependent proteases closely related to caspases. In protozoa, MCA plays an important role in programmed cell death (PCD). In Trichomonas vaginalis, a kind of PCD that resembles apoptosis has been described, but the activators of this mechanism have not been demonstrated.
View Article and Find Full Text PDFNew Brusatol Derivatives as Anti-Settlement Agents Against Barnacles, Targeting HSP90: Design, Synthesis, Biological Evaluation, and Molecular Docking Investigations.
Int J Mol Sci
January 2025
College of Agriculture, Guangxi University, Nanning 530004, China.
The increasing challenge of marine biofouling, mainly due to barnacle settlement, necessitates the development of effective antifoulants with minimal environmental toxicity. In this study, fifteen derivatives of brusatol were synthesized and characterized using C-NMR, H-NMR, and mass spectrometry. All the semi-synthesized compounds obtained using the Multi-Target-Directed Ligand (MTDL) strategy, when evaluated as anti-settlement agents against barnacles, showed promising activity.
View Article and Find Full Text PDFWant AI Summaries of new PubMed Abstracts delivered to your In-box?
Enter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!