Voltage-gated potassium channels play pivotal roles in excitable and non-excitable cells. For many decades, structural properties and molecular mechanisms of these channels were inferred from functional observations. At the turn of the twenty-first century, structural biology revealed major aspects in the structural basis of ion channel organization, permeation, and gating. Among the available tools, homology modeling associated with low resolution microscopy helps in delineating the different structural elements of voltage-gated channels. Here, we describe in detail the methodology of homology modeling, using the 3D structure of the Kv2.1ΔCTA ion channel as a reference.
Download full-text PDF |
Source |
|---|---|
| http://dx.doi.org/10.1007/978-1-4939-7362-0_23 | DOI Listing |
Publication Analysis
Top Keywords
Similar Publications
Repurposing FDA-approved drugs targeting FZD10 in nasopharyngeal carcinoma: insights from molecular dynamics simulations and experimental validation.
Sci Rep
December 2024
Department of Biochemistry, Faculty of Science, Mahidol University, 272 Rama VI Road, Thung Phayathai, Ratchathewi, Bangkok, 10400, Thailand.
Wnt signaling is a critical pathway implicated in cancer development, with Frizzled proteins, particularly FZD10, playing key roles in tumorigenesis and recurrence. This study focuses on the potential of repurposed FDA-approved drugs targeting FZD10 as a therapeutic strategy for nasopharyngeal carcinoma (NPC). The tertiary structure of human FZD10 was constructed using homology modeling, validated by Ramachandran plot and ProQ analysis.
View Article and Find Full Text PDFThe structural influence of the oncogenic driver mutation N642H in the STAT5B SH2 domain.
Protein Sci
January 2025
Department of Physics, University of Toronto, Toronto, Ontario, Canada.
The point mutation N642H of the signal transducer and activator of transcription 5B (STAT5B) protein is associated with aggressive and drug-resistant forms of leukemia. This mutation is thought to promote cancer due to hyperactivation of STAT5B caused by increased stability of the active, parallel dimer state. However, the molecular mechanism leading to this stabilization is not well understood as there is currently no structure of the parallel dimer.
View Article and Find Full Text PDFRestoring adapter protein complex 4 function with small molecules: an in silico approach to spastic paraplegia 50.
Protein Sci
January 2025
Department of Molecular Biotechnology and Health Sciences, University of Torino, Torino, Italy.
This study focuses on spastic paraplegia type 50 (SPG50), an adapter protein complex 4 deficiency syndrome caused by mutations in the adapter protein complex 4 subunit mu-1 (AP4M1) gene, and on the downstream alterations of the AP4M1 protein. We applied a battery of heterogeneous computational resources, encompassing two in-house tools described here for the first time, to (a) assess the druggability potential of AP4M1, (b) characterize SPG50-associated mutations and their 3D scenario, (c) identify mutation-tailored drug candidates for SPG50, and (d) elucidate their mechanisms of action by means of structural considerations on homology models of the adapter protein complex 4 core. Altogether, the collected results indicate R367Q as the mutation with the most promising potential of being corrected by small-molecule drugs, and the flavonoid rutin as best candidate for this purpose.
View Article and Find Full Text PDF(Illiciaceae), an ecologically significant endemic plant, predominantly grows in Guangxi, China, which is the primary region for its cultivation. This area accounts for more than 80% of the total cultivation and yield in China. Despite its importance, comprehensive studies on the chloroplast (cp) genome of are limited.
View Article and Find Full Text PDFDown-regulation of SHP2 promotes neutrophil autophagy and inhibits neutrophil extracellular trap formation to alleviate asthma through the ERK5 pathway.
Cent Eur J Immunol
November 2024
Department of Respiratory Medicine, The Fourth Hospital of Changsha, Changsha, China.
Introduction: Neutrophil autophagy and neutrophil extracellular trap (NET) formation are closely related to asthma pathogenesis. Src homology domain 2-containing protein tyrosine phosphatase 2 (SHP2) is an important regulatory factor in airway remodeling in asthma. This study aimed to explore the molecular mechanisms of SHP2 in neutrophils.
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!