A5049488349- Microbial Natural Products and Biosynthesis
- Plant biochemistry and biosynthesis
- Enzyme Structure and Function
- RNA and protein synthesis mechanisms
- Phytochemistry and Biological Activities
- Natural product bioactivities and synthesis
- Phytochemicals and Antioxidant Activities
- Peptidase Inhibition and Analysis
- Fungal Biology and Applications
- Biological Activity of Diterpenoids and Biflavonoids
- Protein Structure and Dynamics
- Plant Gene Expression Analysis
- RNA Research and Splicing
- Chemical Synthesis and Analysis
- Endoplasmic Reticulum Stress and Disease
- Biochemical and Molecular Research
- Biochemical and biochemical processes
- Genomics and Chromatin Dynamics
Brandeis University
2020-2024
University of Massachusetts Boston
2018-2022
Howard Hughes Medical Institute
2020
The advent of biocatalysts designed computationally and optimized by laboratory evolution provides an opportunity to explore molecular strategies for augmenting catalytic function. Applying a suite nuclear magnetic resonance, crystallography, stopped-flow techniques enzyme elementary proton transfer reaction, we show how directed gradually altered the conformational ensemble protein scaffold populate narrow, highly active accelerate this transformation nearly nine orders magnitude. Mutations...
Most terpene synthase reactions follow Markovnikov rules for formation of high-energy carbenium ion intermediates. However, there are notable exceptions. For example, pentalenene (PS) undergoes an initial anti-Markovnikov cyclization reaction followed by a 1,2-hydride shift to form intermediate humulyl cation with positive charge on the secondary carbon C9 atom farnesyl diphosphate substrate. The mechanism which these enzymes stabilize and guide regioselectivity carbocations has not...
In a continuing effort to understand reaction mechanisms of terpene synthases catalyzing initial anti-Markovnikov cyclization reactions, we solved the X-ray crystal structure (+)-caryolan-1-ol synthase (CS) from
Abstract The HMG-box protein Capicua (CIC) is an evolutionarily conserved transcriptional repressor with key functions in development and disease-associated processes. CIC binds DNA using exclusive mechanism that requires both its a separate domain called C1, but how these domains cooperate to recognize specific sequences not known. Here we report the crystal structure of human C1 complex 18-base-pair oligomer containing consensus octameric binding site. We find adopt independent tri-helical...
In a continuing effort to understand reaction mechanisms of terpene synthases catalyzing initial anti-Markovnikov cyclization reactions, we solved the X-ray crystal structure (+)-caryolan-1-ol synthase (CS) from
The bacterium Yersinia pestis , known for causing the bubonic plague, is an organism which must scavenge free iron from its host to grow. One method of obtaining by producing a siderophore, yersiniabactin (Ybt), secondary metabolite synthesized hybrid polyketide synthase (PKS)/nonribosomal peptide synthetase (NRPS). This system utilizes three interesting heterocyclization (Cy) domains introduce five‐membered rings that are important affinity. research project aims determine molecular...
Many therapeutically useful natural products contain 5‐membered heterocycles derived from either serine, cysteine or threonine, and important examples include the anticancer epothilones bleomycin. In nonribosomal peptide synthetase systems, formation of these rings is catalyzed by a specific functional domain, cyclization (Cy) which catalyzes both bond‐forming condensation reaction subsequent cyclodehydration reaction. To probe mechanism this system, we are exploring Cy domain protein EpoB...
Abstract Most terpene synthase reactions follow Markovnikov rules for formation of high energy carbenium ion intermediates. However, there are notable exceptions. For example, pentalenene (PS) undergoes an initial anti-Markovnikov cyclization reaction followed by a 1,2-hydride shift to form intermediate humulyl cation with positive charge on the secondary carbon C9 farnesyl diphosphate substrate. The mechanism which these enzymes stabilize and guide regioselectivity carbocations has not...