One of the principal goals of the structural genomics initiative is to identify the total repertoire of protein folds and obtain a global view of the "protein structure universe." Here, we present a 3D map of the protein fold space in which structurally related folds are represented by spatially adjacent points. Such a representation reveals a high-level organization of the fold space that is intuitively interpretable. The shape of the fold space and the overall distribution of the folds are defined by three dominant trends: secondary structure class, chain topology, and protein domain size. Random coil-like structures of small proteins and peptides are mapped to a region where the three trends converge, offering an interesting perspective on both the demography of fold space and the evolution of protein structures.
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http://dx.doi.org/10.1073/pnas.2628030100 | DOI Listing |
Nutrients
December 2024
State Key Laboratory of Space Medicine, China Astronaut Research and Training Center, Beijing 100094, China.
Background: Long-term fasting demonstrates greater therapeutic potential and broader application prospects in extreme environments than intermittent fasting.
Method: This pilot study of 10-day complete fasting (CF), with a small sample size of 13 volunteers, aimed to investigate the time-series impacts on gut microbiome, serum metabolome, and their interrelationships with biochemical indices.
Results: The results show CF significantly affected gut microbiota diversity, composition, and interspecies interactions, characterized by an expansion of the Proteobacteria phylum (about six-fold) and a decrease in Bacteroidetes (about 50%) and Firmicutes (about 34%) populations.
Proc Natl Acad Sci U S A
January 2025
Laboratory of Precision Medicine and Biopharmaceuticals, College of Pharmaceutical Sciences, Zhejiang University, Hangzhou 310058, China.
Recurrent missense mutations in the human epidermal growth factor receptor 2 (HER2) have been identified across various human cancers. Among these mutations, the active S310F mutation in the HER2 extracellular domain stands out as not only oncogenic but also confers resistance to pertuzumab, an antibody drug widely used in clinical cancer therapy, by impeding its binding. In this study, we have successfully employed computational-aided rational design to undertake directed evolution of pertuzumab, resulting in the creation of an evolved pertuzumab variant named Ptz-SA.
View Article and Find Full Text PDFAdv Sci (Weinh)
January 2025
State Key Laboratory of Southwestern Chinese Medicine Resources, and Innovative Institute of Chinese Medicine and Pharmacy, Chengdu University of Traditional Chinese Medicine, Chengdu, 611137, P. R. China.
A prolific multi-product sesterterpene synthase CbTPS1 is characterized from the medicinal Brassicaceae plant Capsella bursa-pastoris. Twenty different sesterterpenes including 16 undescribed compounds, possessing 10 different mono-/di-/tri-/tetra-/penta-carbocyclic skeletons, including the unique 15-membered macrocyclic and 24(15→14)-abeo-capbuane scaffolds, are isolated and structurally elucidated from engineered Escherichia coli strains expressing CbTPS1. Site-directed mutagenesis assisted by molecular dynamics simulations resulted in the variant L354M with up to 13.
View Article and Find Full Text PDFNano Lett
January 2025
Department of Materials Science and Engineering, Yonsei University, Seoul 03722, Republic of Korea.
Achieving low thermal conductivity and high mechanical strength presents a material design challenge due to intrinsic trade-offs, such as the aerogel's porosity, impeding applications in construction, industry, and aerospace. This study presents a composite that incorporates a silica aerogel within a thermally expanded 2D layered vermiculite matrix. This design overcomes limitations imposed by van der Waals bonding lengths, typically less than 10 Å, which hinder aerogel integration with van der Waals crystals.
View Article and Find Full Text PDFLaryngoscope Investig Otolaryngol
February 2025
Objectives: This study aimed to investigate the histological and ultrastructural features of the elastic cartilage at the tip of the vocal process in the arytenoid cartilage, which is essential for laryngeal biomechanics.
Methods: Five larynges, including the vocal folds and epiglottis, were examined using transmission electron microscopy. The elastic cartilage at the tip of the vocal process was compared to the epiglottic cartilage within the same larynx to elucidate structural differences.
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