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Electron transfer in polysaccharide monooxygenase catalysis.
Proc Natl Acad Sci U S A
January 2025
California Institute for Quantitative Biosciences, University of California, Berkeley, CA 94720.
Polysaccharide monooxygenase (PMO) catalysis involves the chemically difficult hydroxylation of unactivated C-H bonds in carbohydrates. The reaction requires reducing equivalents and will utilize either oxygen or hydrogen peroxide as a cosubstrate. Two key mechanistic questions are addressed here: 1) How does the enzyme regulate the timely and tightly controlled electron delivery to the mononuclear copper active site, especially when bound substrate occludes the active site? and 2) How does this electron delivery differ when utilizing oxygen or hydrogen peroxide as a cosubstrate? Using a computational approach, potential paths of electron transfer (ET) to the active site copper ion were identified in a representative AA9 family PMO from (PMO9E).
View Article and Find Full Text PDFComputational-aided rational mutation design of pertuzumab to overcome active HER2 mutation S310F through antibody-drug conjugates.
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 PDFAcidic pH can attenuate immune killing through inactivation of perforin.
EMBO Rep
January 2025
Killer Cell Biology Laboratory, Peter MacCallum Cancer Centre, Melbourne, VIC, Australia.
Cytotoxic lymphocytes are crucial to our immune system, primarily eliminating virus-infected or cancerous cells via perforin/granzyme killing. Perforin forms transmembrane pores in the plasma membrane, allowing granzymes to enter the target cell cytosol and trigger apoptosis. The prowess of cytotoxic lymphocytes to efficiently eradicate target cells has been widely harnessed in immunotherapies against haematological cancers.
View Article and Find Full Text PDFDecoding Periorbital Aging: A Multilayered Analysis of Anatomical Changes.
Aesthetic Plast Surg
January 2025
Division of Plastic and Maxillofacial Surgery, Department of Surgery, Ramathibodi Hospital, Mahidol University, Bangkok, Thailand.
Background: Periorbital aging is a complex phenomenon that involves multiple layers of facial anatomy, including bone, fat, and globe. While previous studies have predominantly focused on age-related changes in facial fat compartments, this research aims to provide a comprehensive understanding of all periorbital components, including upper and lower orbital fat, orbital cavity volume, globe volume, and globe position, in the context of aging.
Methods: We conducted a retrospective study involving 118 patients (236 subjects) aged 18-99 years who underwent brain MRI using a 3 Tesla MR system.
Attention modulates subjective time perception across eye movements.
Vision Res
January 2025
Center for Psychological Science, Zhejiang University, Hangzhou, China.
Prior research has established that actions, such as eye movements, influence time perception. However, the relationship between pre-saccadic attention, which is often associated with eye movement, and subjective time perception is not explored. Our study examines the impact of pre-saccadic attention on the subjective experience of time during eye movements, particularly focusing on its influence on subjective time perception at the saccade target.
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