A5080013174- Metalloenzymes and iron-sulfur proteins
- CO2 Reduction Techniques and Catalysts
- Enzyme Structure and Function
- Clostridium difficile and Clostridium perfringens research
- Ammonia Synthesis and Nitrogen Reduction
- Gut microbiota and health
- Microbial Metabolic Engineering and Bioproduction
- Electrocatalysts for Energy Conversion
- Porphyrin Metabolism and Disorders
- Pharmacological Effects of Natural Compounds
- Interdisciplinary Research and Collaboration
- Click Chemistry and Applications
- Metabolism and Genetic Disorders
- Metal-Catalyzed Oxygenation Mechanisms
- Advanced Photocatalysis Techniques
- Amino Acid Enzymes and Metabolism
- Sulfur Compounds in Biology
- Nitrogen and Sulfur Effects on Brassica
- Fluoride Effects and Removal
- Cancer, Hypoxia, and Metabolism
- Pediatric health and respiratory diseases
- Biomedical and Engineering Education
- RNA modifications and cancer
- NF-κB Signaling Pathways
- Hemoglobin structure and function
Whitehead Institute for Biomedical Research
2024
Massachusetts Institute of Technology
2017-2022
IIT@MIT
2022
University of Florida
2015-2017
Nature has devised an array of enzymatic cofactors that enable challenging chemical transformations to occur on a timescale compatible with biological life. Protein-based amino acid radicals are one example simple yet powerful radical cofactor capable catalyzing diverse chemistry. The glycyl enzyme (GRE) superfamily is prominent this type and the catalytic power it possesses. GREs use housed a-carbon glycine residue in active site perform catalysis anaerobic environments. radical-storing...
Despite living in an oxygen-filled world, anaerobic bacteria are abundant; there many oxygen-scarce sites the human microbiome, including gut, mouth, and even skin pores. Under low-oxygen conditions, rely on oxygen- sensitive enzymes to carry out metabolic processes critical for survival, yet microbiome vulnerable oxygen or oxidative stress. Our nascent lab explores molecular tactics that gut anaerobes protect such pathways carrying states, potentially providing a competitive advantage these...
Reduced ATM function has been linked to breast cancer risk, and the TRIM29 protein is an emerging tumor suppressor. Here we show that, in cultured non-tumorigenic mammary epithelial cells, up-regulated response hypoxic stress but not DNA damage. Hypoxia-induced up-regulation of dependent upon HIF1α occurs through increased transcription gene. Basal expression also down-regulated cells expressing diminished levels ATM, findings suggest that this basal NF-κB activity as knockdown subunit RelA...
The glycyl radical enzyme (GRE) superfamily utilizes a cofactor to catalyze difficult chemical reactions in variety of anaerobic microbial metabolic pathways. Recently, GRE, trans-4-hydroxy-L-proline (Hyp) dehydratase (HypD), was discovered that catalyzes the dehydration Hyp (S)-Δ1-pyrroline-5-carboxylic acid (P5C). This is abundant human gut microbiome and also present prominent bacterial pathogens. However, we lack an understanding how HypD performs its unusual chemistry. Here, have solved...
Desulfonation of isethionate by the bacterial glycyl radical enzyme (GRE) sulfite-lyase (IslA) generates sulfite, a substrate for respiration that in turn produces disease-associated metabolite hydrogen sulfide. Here, we present 2.7 Å resolution X-ray structure wild-type IslA from Bilophila wadsworthia with bound. In comparison other GREs, alternate positioning active site β strands allows distinct residue positions to contribute binding. These structural differences, combined sequence...
Nature has devised an array of enzymatic cofactors that enable challenging chemical transformations to occur on a timescale compatible with biological life. Radical are commonly utilized accomplish such chemistry-their high reactivity allows for would be inaccessible otherwise. Protein-based amino acid radicals one example simple yet powerful radical cofactor capable catalyzing diverse chemistry. The glycyl enzyme (GRE) superfamily is prominent this type and the catalytic power it possesses....
Despite living in an oxygen-filled world, anaerobic bacteria are abundant; there many oxygen-scarce sites the human microbiome, most notably gut. Under low-oxygen conditions, rely on oxygen-sensitive enzymes to carry out metabolic processes critical for survival. Our lab explores molecular tactics that gut anaerobes protect such pathways vulnerable oxidative damage and thrive amidst stress, potentially providing a competitive advantage these microbes. One potential strategy is physically...
Desulfonation of isethionate by the bacterial glycyl radical enzyme (GRE) sulfite-lyase (IslA) generates sulfite, a substrate for sulfite respiration that in turn produces disease-associated metabolite hydrogen sulfide. Here, we present 2.7 Å resolution X-ray structure wild-type IslA from Bilophila wadsworthia with bound. In comparison to other GREs, alternate positioning active site β strands allows distinct residue positions contribute binding. These structural differences combined...
Microbiome research has rapidly advanced through the use of high‐through put sequencing technologies, but functions most genes in sequence databases remain unknown. Glycyl radical enzymes represent an ancient protein super family, which is one abundant families human gut microbiome. These chemistry to catalyze a diverse set chemically difficult transformations metabolic pathways essential for anaerobic growth. Here, we describe biochemical characterization new member glycyl enzyme...
Glycyl radical enzymes (GREs) employ a post-translationally installed glycyl species to carry out wide range of chemistry in bacteria. The cofactor is simple and effective catalyst, but it has an Achilles' heel - susceptible cleavage by molecular oxygen. For this reason, GREs are commonly expressed bacteria under anoxic conditions, not exclusively. most well studied GRE, pyruvate formate lyase (PFL), constitutively expressed, enzyme acts primary metabolism, converting coenzyme A into...
The glycyl radical enzyme (GRE) family utilizes a cofactor, installed by AdoMet activating enzymes, to catalyze difficult chemical reactions in variety of microbial metabolic pathways. Although GREs are widely encoded and expressed bacteria found the gut microbiome, these enzymes remain largely uncharacterized. Recently new GRE, hydroxyproline dehydratase (HypD) was discovered dehydration trans-4-hydroxy-L-proline (4-Hyp) 1-pyrroline-5-carboxylic acid. HypD is second most prominent GRE human...