A5009275741- DNA Repair Mechanisms
- Bacterial Genetics and Biotechnology
- Herpesvirus Infections and Treatments
- Protease and Inhibitor Mechanisms
- Cancer therapeutics and mechanisms
- Toxin Mechanisms and Immunotoxins
- Diet and metabolism studies
- Viral Infections and Immunology Research
- HIV/AIDS oral health manifestations
- RNA Interference and Gene Delivery
- Blood Coagulation and Thrombosis Mechanisms
- Antifungal resistance and susceptibility
- Fungal Infections and Studies
- Cytomegalovirus and herpesvirus research
- Plant Virus Research Studies
- DNA and Nucleic Acid Chemistry
- CRISPR and Genetic Engineering
- Tryptophan and brain disorders
- Advanced biosensing and bioanalysis techniques
- Genomics and Chromatin Dynamics
- Transgenic Plants and Applications
- Gut microbiota and health
- Plant tissue culture and regeneration
- Antibiotic Resistance in Bacteria
- Enzyme Structure and Function
University of York
2024
Harvard University
2017-2024
New York State Department of Health
2013-2021
University at Albany, State University of New York
2013-2021
Wadsworth Center
2013-2021
Scripps Research Institute
2018-2020
Scripps Institution of Oceanography
2020
Scripps (United States)
2020
Midnapore Medical College and Hospital
2017
DNA polymerases are important drug targets, and many structural studies have captured them in distinct conformations. However, a detailed understanding of the impact polymerase conformational dynamics on resistance is lacking. We determined cryoelectron microscopy (cryo-EM) structures DNA-bound herpes simplex virus holoenzyme multiple conformations interacting with antivirals clinical use. These reveal how catalytic subunit Pol processivity factor UL42 bind to promote processive synthesis....
Although the functional specificity and catalytic versatility of enzymes have been exploited in numerous settings, controlling spatial temporal activity remains challenging. Here we describe an approach for programming function streptokinase (SK), a protein that is clinically used as blood "clot buster" therapeutic. We show fibrinolytic resulting from binding SK to plasma proenzyme plasminogen (Pg) can be effectively regulated (turned "OFF" "ON") by installing intrasteric regulatory feature...
Polymerases belonging to the DinB class of Y-family translesion synthesis DNA polymerases have a preference for accurately and efficiently bypassing damaged guanosines. These also generate single-base (-1) deletions at high frequencies with most occurring on repetitive 'deletion hotspot' sequences. Human polymerase kappa (hPolκ), eukaryotic homologue, displays an unusual efficiency extend from mispaired primer termini, either by extending directly mispair or primer-template misalignment....
PolC is the C-family replicative polymerase in low G+C content Gram-positive bacteria. To date several structures of polymerases have been reported, including a high resolution crystal structure ternary complex with DNA and incoming deoxynucleoside triphosphate (dNTP). However, kinetic information needed to understand enzymatic mechanism limited. For this study we performed detailed steady-state pre-steady-state characterization correct dNTP incorporation by from pathogen Staphylococcus...
Bacterial replication is a fast and accurate process, with the bulk of genome duplication being catalyzed by α subunit DNA polymerase III within bacterial replisome. Structural biochemical studies have elucidated overall properties these polymerases, including how they interact other components replisome, but only begun to define enzymatic mechanism nucleotide incorporation. Using transient-state methods, we determined kinetic PolC, replicative from Gram-positive pathogen Staphylococcus...
The catalytic subunit (Pol) of herpes simplex virus 1 (HSV-1) DNA polymerase has been extensively studied both as a model for other family B polymerases and its differences from these enzymes an antiviral target. Among the activities HSV-1 Pol is intrinsic RNase H activity that cleaves RNA RNA-DNA hybrids. There long controversy regarding whether this due to 3'-to-5' exonuclease or it separate activity, possibly acting on 5' termini. To investigate issue, we compared wild-type...
A recombinant engineered variant of APC (activated protein C), 3K3A-APC, lacks anticoagulant properties (<10%) while preserving APCs anti-inflammatory, anti-apoptotic, and neuroprotective functions is very promising in clinical trials for ischemic stroke. Therapeutic intervention with single bolus administration the third-generation tPA (tissue-type plasminogen activator), tenecteplase, anticipated to be widely adopted treatment acute 3K3A-APC well-tolerated stroke patients dosed alteplase,...
As evidence points to the use of multiple DNA pol III’s by gram‐positive bacteria, a question remains: which biochemical factors (domain composition, oligonucleotide (oligo) length, etc.) serve as strongest determinants fidelity? We have characterized various patterns relative mutagenicity amongst essential C‐family bacterial polymerases found in Staphylococcus aureus. These include two PolC constructs: PolC‐Exomut and PolC‐ΔNΔExo, well DnaE. In vitro assays were performed using...
The opportunistic mycoses are those fungal infections which found in patients whose immunological defence mechanisms weakened by cancer,AIDS, etc.In patient with AIDS, incidence of inversely correlated the CD4 lymphocyte count.Our aim was to establish a correlation between and CD4+ T cell count, evaluate prevalence HIV , correlate speciation count .SDA, SDCA, SDCCA were used as isolation culture media.Moulds their species identified colony morphology Teasing LCB mount findings.Candida spp....