A5100780291- Biochemical and Molecular Research
- Enzyme Structure and Function
- Colorectal Cancer Treatments and Studies
- Biochemical Acid Research Studies
- HIV/AIDS drug development and treatment
- Cancer, Hypoxia, and Metabolism
- Chemical Synthesis and Analysis
- Seed Germination and Physiology
- DNA Repair Mechanisms
- Cancer Research and Treatments
- Protein Structure and Dynamics
- Neonatal Health and Biochemistry
- Genetic factors in colorectal cancer
- Rice Cultivation and Yield Improvement
- Fluorine in Organic Chemistry
- Plant tissue culture and regeneration
- Supramolecular Self-Assembly in Materials
- Infant Nutrition and Health
- Radiopharmaceutical Chemistry and Applications
- Porphyrin Metabolism and Disorders
- RNA Interference and Gene Delivery
- Analytical Chemistry and Chromatography
University of Iowa
2013-2018
Iowa City Public Library
2015
Shizuoka University
2013
University of Dhaka
1997
Kinetic Isotope effects (KIEs) have long served as a probe for the mechanisms of both enzymatic and solution reactions. Here, we discuss various models physical sources KIEs, how experimentalists can use those to interpret their data, focus traditional has grown model that includes motion enzyme quantum mechanical nuclear tunneling. We then present two case studies enzymes, thymidylate synthase alcohol dehydrogenase, KIEs shed light on C-H bond cleavages enzymes catalyze. will show...
Thymidylate synthase (TSase) catalyzes the intracellular de novo formation of thymidylate (a DNA building block) in most living organisms, making it a common target for chemotherapeutic and antibiotic drugs. Two mechanisms have been proposed rate-limiting hydride transfer step TSase catalysis: stepwise mechanism which precedes cleavage covalent bond between enzymatic cysteine product where both happen concertedly. Striking similarities enzyme-bound enolate intermediates formed initial final...
Thymidylate Synthase (TSase) is a highly conserved enzyme that catalyzes the production of DNA building block thymidylate. Structurally, functionally and mechanistically, bacterial mammalian TSases share remarkable similarities. Because this closeness, enzymes have long been used as model systems for human TSase. Furthermore, while TSase inhibitors served chemotherapeutic drugs, no inhibitor serves an antibiotic. Despite their high resemblance, are distinct in few known aspects, such having...
The temperature dependence of intrinsic KIE studies reveal Y94 as a component the general base facilitating proton abstraction step.
Thymidylate synthase (TSase) catalyzes the de novo biosynthesis of thymidylate, a precursor for DNA, and is thus an important target chemotherapeutics antibiotics. Two sequential C–H bond cleavages catalyzed by TSase are particular interest: reversible proton abstraction from 2′-deoxyuridylate substrate, followed irreversible hydride transfer forming thymidylate product. QM/MM calculations former predicted mechanism in which leads to formation novel nucleotide-folate intermediate that not...
Thymidylate synthase (TSase), an enzyme responsible for the de novo biosynthesis of 2′-deoxythymidine 5′-monophosphate (thymidylate, dTMP) necessary DNA synthesis, has been a drug target decades. TSase is highly conserved across species ranging from very primitive organisms to mammals. Among many active site residues, asparagine (N177, using Escherichia coli residues numbering) appears make direct hydrogen bonds with both C4═O4 carbonyl 2′-deoxyuridine (uridylate, dUMP) substrate and its...
Thymidylate Synthase (TSase) is a crucial enzyme that maintains cellular dTMP (2′-deoxythymidine-5′-monophosphate) pool required for DNA biosynthesis in most living organisms. TSases requires the cofactor methylene tetrahydrofolate (CH2H4folate) donates and subsequently hydride to substrate dUMP (2′-deoxyuridine-5′-monophosphate) form dTMP. Two sequential H-transfers are at heart of TSase catalysis: non rate-limiting proton abstraction from carbon transfer between two carbons. QM/MM...
Thymidylate synthase (TSase, EC 2.1.1.45) catalyzes the reductive methylation of 2′-deoxyuridine-5′-monophosphate (dUMP) to form 2′-deoxythymidine-5′-monophosphate (dTMP), one precursor DNA bases. Many chemotherapeutic drugs target TSase as it is essential for de novo biosynthesis in nearly all organisms including human. Although there are two different C-H bond activation throughout mechanism, contrast well resolved mechanism hydride transfer step, identity general base that abstract proton...
Abstract Review: 95 refs.
Thymidylate Synthase (TSase) is an enzyme that converts 2′‐deoxyuridinemonophosphate (dUMP) to thymidylate (dTMP), a base for DNA. Since there no other de novo route dTMP in cells, TSase critical cell replication and survival. 5F‐dUMP – produced intracellularly from the chemotherapeutic pro‐drug 5‐fluorouracil (5‐FU) inhibits TSase, thus halting supply of DNA thymidylate, causing cessation synthesis leading thymine‐less death. While it very common pathogenic organisms become resistant...