The lytic polysaccharide monooxygenases (LPMOs) comprise a super-family of copper enzymes that boost the depolymerisation of polysaccharides by oxidatively disrupting the glycosidic bonds connecting the sugar units. Industrial use of LPMOs for cellulose depolymerisation has already begun but is still far from reaching its full potential. One issue is that the LPMOs self-oxidise and thereby deactivate. The mechanism of this self-oxidation is unknown, but histidine residues coordinating to the copper atom are the most susceptible. An unusual methyl modification of the NE2 atom in one of the coordinating histidine residues has been proposed to have a protective role. Furthermore, substrate binding is also known to reduce oxidative damage. We here for the first time investigate the mechanism of histidine oxidation with combined quantum and molecular mechanical (QM/MM) calculations, with outset in intermediates previously shown to form from a reaction with peroxide and a reduced LPMO. We show that an intermediate with a [Cu-O] moiety is sufficiently potent to oxidise the nearest C-H bond on both histidine residues, but methylation of the NE2 atom of His-1 increases the reaction barrier of this reaction. The substrate further increases the activation barrier. We also investigate a [Cu-OH] intermediate with a deprotonated tyrosine radical. This intermediate was previously proposed to have a protective role, and we also find it to have higher barriers than the corresponding a [Cu-O] intermediate.
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http://dx.doi.org/10.1007/s00775-023-01993-4 | DOI Listing |
Biomacromolecules
January 2025
Department of Chemistry, Rice University, Houston, Texas 77005, United States.
In this work, we investigate the pH-responsive behavior of multidomain peptide (MDP) hydrogels containing histidine. Small-angle X-ray scattering confirmed that MDP nanofibers sequester nonpolar residues into a hydrophobic core surrounded by a shell of hydrophilic residues. MDPs with histidine on the hydrophilic face formed nanofibers at all pH values tested, but the morphology of the fibers was influenced by the protonation state and the location of histidine in the MDP sequence.
View Article and Find Full Text PDFNat Commun
January 2025
Shanghai Frontiers Science Center of Genome Editing and Cell Therapy, Shanghai Key Laboratory of Regulatory Biology, Institute of Biomedical Sciences and School of Life Sciences, East China Normal University, Shanghai, China.
Am J Hum Genet
January 2025
Institute of Human Genetics, University Medical Center Hamburg-Eppendorf, 20246 Hamburg, Germany; Institute of Human Genetics, University of Regensburg, 93053 Regensburg, Germany; Institute of Clinical Human Genetics, University Hospital Regensburg, 93053 Regensburg, Germany. Electronic address:
BCL11B is a Cys2-His2 zinc-finger (C2H2-ZnF) domain-containing, DNA-binding, transcription factor with established roles in the development of various organs and tissues, primarily the immune and nervous systems. BCL11B germline variants have been associated with a variety of developmental syndromes. However, genotype-phenotype correlations along with pathophysiologic mechanisms of selected variants mostly remain elusive.
View Article and Find Full Text PDFInt J Biol Macromol
January 2025
Centro de Investigación Biomédica en Red de Bioingeniería, Biomateriales y Nanomedicina, Instituto de Salud Carlos III, Barcelona, Spain; Departament de Genètica i de Microbiologia, Universitat Autònoma de Barcelona, Barcelona, Spain; Biomedical Research Institute Sant Pau (IR Sant Pau), Barcelona, Spain. Electronic address:
In nature, nontoxic protein amyloids serve as dynamic, protein-specific depots, exemplified by both bacterial inclusion bodies and secretory granules from the endocrine system. Inspired by these systems, chemically defined and regulatory-compliant artificial protein microgranules have been developed for clinical applications as endocrine-like protein repositories. This has been achieved by exploiting the reversible coordination between histidine residues and divalent cations such as Zn, that promotes protein-protein interactions.
View Article and Find Full Text PDFFood Chem
January 2025
Institute of Food Science and Technology, Chinese Academy of Agricultural Sciences/Key Laboratory of Agricultural Product Processing, Ministry of Agriculture, Beijing 100193, China; Zibo Institute for Digital Agriculture and Rural Research, Zibo 255051, China. Electronic address:
The study was designed to investigate the mechanism of Riboflavin (RF)-mediated UVA photosensitive oxidation on beef myofibrillar proteins (MP) oxidized at different storage times. To elucidate the direct relationship between RF and protein oxidation, the mechanism of action was analyzed in terms of amino acid and side chain residues, protein structure, and protein oxidative metabolism. Oxidation of MP resulted in significant changes in the levels of carbonyls, sulfhydryls, Lysine, Arginine, Threonin, and Histidine.
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