Computational assessment of the IL-17A structure identified two distinct binding pockets, the β-hairpin pocket and the α-helix pocket. The β-hairpin pocket was hypothesized to be the site of binding for peptide macrocycles. Support for this hypothesis was obtained using HDX-MS which revealed protection to exchange only within the β-hairpin pocket. This data represents the first direct structural evidence of a small molecule binding site on IL-17A that functions to disrupt the interaction with its receptor.
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http://dx.doi.org/10.1021/acs.jmedchem.5b01693 | DOI Listing |
BMC Oral Health
January 2025
Dentistry and Maxillo-Facial Surgery Unit, Department of Surgery, Dentistry, Paediatrics and Gynaecology (DIPSCOMI), University of Verona, Piazzale L.A. Scuro 10, 37134, Verona, Italy.
Introduction: Orofacial cleft impacts jawbone and dental development and function, often with consequences for oral health. The first in this two-part systematic review of the literature on oral health in persons with cleft lip and/or palate focuses on periodontal parameters and composition of oral bacterial flora, while the second analyzes data on dental caries.
Materials And Methods: Four databases (PubMed, Cochrane, Scopus, Web of Science) were searched for studies that compared periodontal parameters, caries index, and microbiota composition between persons with cleft lip and/or palate and healthy controls.
BMC Public Health
January 2025
Centre for Healthcare Management, Administrative Staff College of India (ASCI), Hyderabad, India.
Background: Substantial out-of-pocket (OOP) expenditures push a large portion of the population below the poverty line, especially those residing in rural areas having low incomes. Individuals from economically disadvantaged states in India incur higher healthcare costs for hospitalization in public health centers than do those from more developed states. Economically poorer households in states such as Bihar and Odisha face significantly higher OOP expenditures for hospitalization in public health centers than do those in economically developed states such as Tamil Nadu.
View Article and Find Full Text PDFAMB Express
January 2025
Department of Microbiology and Immunology, Faculty of Pharmacy, Zagazig University, Zagazig, 44519, Egypt.
Candida albicans is a commensal fungus that naturally inhabits the vagina. However, overgrowth of C. albicans can result in vulvovaginal candidiasis (VVC), one of the most prevalent fungal infections affecting women.
View Article and Find Full Text PDFNature
January 2025
Department of Molecular Biology, University of Texas Southwestern Medical Center, Dallas, TX, USA.
γ-Glutamyl carboxylase (GGCX) is the sole identified enzyme that uses vitamin K (VK) as a cofactor in humans. This protein catalyses the oxidation of VK hydroquinone to convert specific glutamate residues to γ-carboxyglutamate residues in VK-dependent proteins (VDPs), which are involved in various essential biological processes and diseases. However, the working mechanism of GGCX remains unclear.
View Article and Find Full Text PDFNature
January 2025
Institute of Molecular Health Sciences, Department of Biology, Swiss Federal Institute of Technology (ETH) Zurich, Zurich, Switzerland.
During normal cellular homeostasis, unfolded and mislocalized proteins are recognized and removed, preventing the build-up of toxic byproducts. When protein homeostasis is perturbed during ageing, neurodegeneration or cellular stress, proteins can accumulate several forms of chemical damage through reactive metabolites. Such modifications have been proposed to trigger the selective removal of chemically marked proteins; however, identifying modifications that are sufficient to induce protein degradation has remained challenging.
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