A5102733160- Glycosylation and Glycoproteins Research
- Ubiquitin and proteasome pathways
- RNA and protein synthesis mechanisms
- Monoclonal and Polyclonal Antibodies Research
- Tuberculosis Research and Epidemiology
- Peptidase Inhibition and Analysis
- Chemical Synthesis and Analysis
- Carbohydrate Chemistry and Synthesis
- RNA modifications and cancer
- Genomics and Chromatin Dynamics
- Inorganic and Organometallic Chemistry
- Click Chemistry and Applications
- Cancer-related gene regulation
- CRISPR and Genetic Engineering
- Synthesis and Reactivity of Heterocycles
- Insect symbiosis and bacterial influences
- Axon Guidance and Neuronal Signaling
- S100 Proteins and Annexins
- Bacteriophages and microbial interactions
- Protein Kinase Regulation and GTPase Signaling
- Phenothiazines and Benzothiazines Synthesis and Activities
- Protein Degradation and Inhibitors
- Cyclopropane Reaction Mechanisms
- Free Radicals and Antioxidants
- Epigenetics and DNA Methylation
University of Oxford
2014-2024
University of North Texas
2024
University of North Texas Health Science Center
2024
Immunocore (United Kingdom)
2024
Lovely Professional University
2023
Indian Institute of Science Education and Research Kolkata
2010
Posttranslational modification of proteins expands their structural and functional capabilities beyond those directly specified by the genetic code. However, vast diversity chemically plausible (including unnatural but functionally relevant) side chains is not readily accessible. We describe C (sp3)-C (sp3) bond-forming reactions on under biocompatible conditions, which exploit unusual carbon free-radical chemistry, use them to form Cβ-Cγ bonds with altered chains. demonstrate how these...
Abstract Glycosylation patterns in antibodies critically determine biological and physical properties but their precise control is a significant challenge biology biotechnology. We describe herein the optimization of an endoglycosidase‐catalyzed glycosylation best‐selling biotherapeutic Herceptin, anti‐HER2 antibody. Precise MS analysis intact four‐chain Ab heteromultimer reveals nonspecific, non‐enzymatic reactions (glycation), which are not detected under standard denaturing conditions....
We describe palladium-mediated S-arylation that exploits natural metal-binding motifs to ensure high site selectivity for a proximal reactive residue. This allows the chemical identification not only of proteins bind metals but also environment itself through proteomic analysis arylation sites. The transformation is easy perform under standard conditions, does require isolation Ar-Pd complex, broad in scope, and applicable cell lysates as well covalent inhibition/modulation metal-dependent...
Enzyme-mediated damage repair or mitigation, while common for nucleic acids, is rare proteins. Examples of protein are elimination phosphorylated Ser/Thr to dehydroalanine/dehydrobutyrine (Dha/Dhb) in pathogenesis and aging. Bacterial LanC enzymes use Dha/Dhb form carbon-sulfur linkages antimicrobial peptides, but the functions eukaryotic LanC-like (LanCL) counterparts unknown. We show that LanCLs catalyze addition glutathione proteins, driving irreversible C-glutathionylation....
Abstract O- GlcNAcylation is a newly discovered histone modification implicated in transcriptional regulation, but no structural information on the physical effect of chromatin exists. Here, we generate synthetic, pure GlcNAcylated histones and nucleosomes reveal that can modulate structure through direct destabilization H2A/H2B dimers nucleosome, thus promoting an ‘open’ state. The results suggest plausible molecular basis for one role O -GlcNAcylation epigenetic regulation to lower barrier...
Abstract Tuberculosis remains a large global disease burden for which treatment regimens are protracted and monitoring of activity difficult. Existing detection methods rely almost exclusively on bacterial culture from sputum limits sampling to organisms the pulmonary surface. Advances in tuberculous lesions have utilized common glucoside [ 18 F]FDG, yet lack specificity causative pathogen Mycobacterium tuberculosis ( Mtb ) so do not directly correlate with viability. Here we show that close...
Through a "tag-and-modify" protein chemical modification strategy, we site-selectively phosphorylated the activation loop of kinase p38α. Phosphorylation at natural (180) and unnatural (172) sites created two pure phospho-forms. p38α bearing only single phosphocysteine (pCys) as mimic pThr 180 was sufficient to switch an active state, capable processing substrate ATF2; 172 site phosphorylation did not. In this way, chemically recapitulated triggering relevant segment MAPK-signaling pathway...
Abstract The desire to study biology in situ has been aided by many imaging techniques. Among these, X-ray fluorescence (XRF) mapping permits observation of elemental distributions a multichannel manner. However, XRF is underused, part, because the difficulty interpreting maps without an underlying cellular ‘blueprint’; this could be supplied using contrast agents. Carbon nanotubes (CNTs) can filled with wide range inorganic materials, and thus used as ‘contrast agents’ if biologically...
Transcriptional regulation can be established by various post-translational modifications (PTMs) on histone proteins in the nucleosome and nucleobase chromosomal DNA. Functional consequences of O-GlcNAcylation (O-GlcNAc=O-linked β-N-acetylglucosamine) are largely unexplored. Herein, we generate homogeneously GlcNAcylated histones nucleosomes chemical modification. Mass-spectrometry-based quantitative interaction proteomics reveals a direct between "facilitates chromatin transcription" (FACT)...
Virus-like particles (VLPs) are stable protein cages derived from virus coats. They have been used extensively as biomolecular platforms, e.g., nanocarriers or vaccines, but a convenient in situ technique is lacking for tracking functional status. Here, we present simple way to monitor disassembly of
Abstract Glycosylation patterns in antibodies critically determine biological and physical properties but their precise control is a significant challenge biology biotechnology. We describe herein the optimization of an endoglycosidase‐catalyzed glycosylation best‐selling biotherapeutic Herceptin, anti‐HER2 antibody. Precise MS analysis intact four‐chain Ab heteromultimer reveals nonspecific, non‐enzymatic reactions (glycation), which are not detected under standard denaturing conditions....
Significance Microbial resistance to β-lactam antibiotics mediated by β-lactamase–catalyzed hydrolysis is a major global health concern. Penam sulfones, which are structurally related penicillins, inhibit clinically important serine β-lactamases (SBLs) forming transiently stable covalent complexes, thereby protecting from hydrolysis. The characterization of these complexes and mechanisms SBL inhibition for development new inhibitors (SBLi). Studies on the mechanism SBLi enmetazobactam...
Tuberculosis remains a large global disease burden for which treatment regimens are protracted and monitoring of activity difficult. Existing detection methods rely almost exclusively on bacterial culture from sputum limits sampling to organisms the pulmonary surface. Advances in tuberculous lesions have utilized common glucoside [
The kinetics of oxidation amino acids (S) by peroxomonosulphate (PMS) in the presence formaldehyde (SH) were studied. Analysis results shows that rate can be represented equation (i), at constant [H+]. effect hydrogen ion on and thermodynamic, –d[PMS]/dt=k′[S][SH][PMS]+k″[SH][PMS](i) parameters was also calculated. Perusal kinetic first step reaction with PMS is formation a Schiff's base. This base reacts more rapidly rate-determining to give products. mechanism discussed terms results.
Abstract Transcriptional regulation can be established by various post‐translational modifications (PTMs) on histone proteins in the nucleosome and nucleobase chromosomal DNA. Functional consequences of O‐GlcNAcylation (O‐GlcNAc=O‐linked β‐N‐acetylglucosamine) are largely unexplored. Herein, we generate homogeneously GlcNAcylated histones nucleosomes chemical modification. Mass‐spectrometry‐based quantitative interaction proteomics reveals a direct between “facilitates chromatin...
SUMMARY The stability and abundance of spliceosomal snRNPs are determined by the assembly an Sm protein ring (Sm core) on each snRNA, a process facilitated survival motor neuron (SMN) complex. Whereas SMN complex’s role as chaperone is well-established, mechanisms that regulate its activity remain unclear. Our study identifies U1C, U1 snRNP-specific protein, key regulator U1C together with U1-70K facilitates snRNP formation, rendering complex accessible for other snRNAs to assemble cores....
Abstract The non-polymorphic HLA-E molecule offers opportunities for new universal immunotherapeutic approaches to chronic infectious diseases. Chronic Hepatitis B virus (HBV) infection is driven in part by T cell dysfunction due elevated levels of the HBV envelope (Env) protein hepatitis surface antigen (HBsAg). Here we report characterization three genotypic variants an HLA-E-binding HBsAg peptide, Env 371-379, identified through bioinformatic predictions and verified biochemical cellular...
The field of life science research has undergone a revolution thanks to the CRISPR (Clustered Regularly Interspaced Short Palindromic Repeats) and CRISPR-associated protein (CRISPR/Cas) system, which provides multitude opportunities for modifying, identifying, visualising, annotating particular DNA or RNA sequences in diverse organisms. In this technique, foreign pieces, known as spacers, are inserted into cassettes. These spacers then transcribed arrays processed produce guide (gRNA). Cas...
In small molecule organic chemistry, the heuristic insight into ring-forming processes that was enabled by Baldwin's rules some 50 years ago proved a step-change in role of mechanistically guided synthesis. It created lens upon and marker fundamental stereoelectronic conformation-guided chemical processes. However, despite widespread stereoelectronics conformational control Biology, no equivalent coherent exploitation trapped, yet exists biomolecules. development minimal ring-closing process...
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Summary Neural migration is a critical step during brain development that requires the interactions of cell-surface guidance receptors. Cancer cells often hijack these mechanisms to disseminate. Here we reveal crystal structures Uncoordinated-5 receptor D (Unc5D) in complex with morphogen glypican-3 (GPC3), forming an octameric glycoprotein complex. In complex, four Unc5D molecules pack into antiparallel bundle, flanked by GPC3 molecules. Central glycan-glycan are formed N-linked glycans...