A5042290896- Heme Oxygenase-1 and Carbon Monoxide
- Metal-Catalyzed Oxygenation Mechanisms
- Photosynthetic Processes and Mechanisms
- Hemoglobin structure and function
- Toxin Mechanisms and Immunotoxins
- Streptococcal Infections and Treatments
- Epigenetics and DNA Methylation
- Enzyme Catalysis and Immobilization
- Microbial metabolism and enzyme function
- Chemical Synthesis and Analysis
- Porphyrin Metabolism and Disorders
- Gut microbiota and health
- bioluminescence and chemiluminescence research
- Microbial Metabolic Engineering and Bioproduction
- Biotin and Related Studies
- PARP inhibition in cancer therapy
- Computational Drug Discovery Methods
- Carbohydrate Chemistry and Synthesis
- Tryptophan and brain disorders
- Biochemical and Molecular Research
- Calcium signaling and nucleotide metabolism
- Enzyme Production and Characterization
- Chemical Reactions and Isotopes
- Sirtuins and Resveratrol in Medicine
- Cyclopropane Reaction Mechanisms
University of Manchester
2015-2024
Czech Academy of Sciences, Institute of Biotechnology
2016
The catalytic versatility of pentacoordinated iron is highlighted by the broad range natural and engineered activities heme enzymes such as cytochrome P450s, which position a porphyrin cofactor coordinating central atom below an open substrate binding pocket. This prowess has inspired efforts to design de novo helical bundle scaffolds that bind cofactors. However, designs lack large pocket hence, chemical transformations accessible limited. Here, with goal combining advantages P450 site...
Sirtuins are an ancient family of NAD(+)-dependent deacylases connected with the regulation fundamental cellular processes including metabolic homeostasis and genome integrity. We show existence a hitherto unrecognized class sirtuins, found predominantly in microbial pathogens. In contrast to earlier described classes, these sirtuins exhibit robust protein ADP-ribosylation activity. our model organisms, Staphylococcus aureus Streptococcus pyogenes, activity is dependent on prior lipoylation...
Abstract Enzyme design and engineering strategies are typically constrained by the limited size of nature’s genetic alphabet, comprised only 20 canonical amino acids. In recent years, site-selective incorporation non-canonical acids (ncAAs) via an expanded code has emerged as a powerful means inserting new functional components into proteins, with hundreds structurally diverse ncAAs now available. Here, we highlight how emergence repertoire opened avenues in enzyme engineering. have been...
Nature employs a limited number of genetically encoded axial ligands to control diverse heme enzyme activities. Deciphering the functional significance these requires quantitative understanding how their electron-donating capabilities modulate structures and reactivities iconic ferryl intermediates compounds I II. However, probing relationships experimentally has proven be challenging as ligand substitutions accessible via conventional mutagenesis do not allow fine tuning electron donation...
Nature employs high-energy metal-oxo intermediates embedded within enzyme active sites to perform challenging oxidative transformations with remarkable selectivity. Understanding how different local coordination environments control intermediate reactivity and catalytic function is a long-standing objective. However, conducting structure-activity relationships directly in has proven due the limited range of amino acid substitutions achievable constraints genetic code. Here, we use an...
The ability to introduce noncanonical amino acids as axial ligands in heme enzymes has provided a powerful experimental tool for studying the structure and reactivity of their FeIV═O ("ferryl") intermediates. Here, we show that similar approach can be used perturb conserved Fe coordination environment 2-oxoglutarate (2OG) dependent oxygenases, versatile class employ highly-reactive ferryl intermediates mediate challenging C–H functionalizations. Replacement one cis-disposed histidine...