Open Access. Powered by Scholars. Published by Universities.®

Enzymes and Coenzymes Commons

Open Access. Powered by Scholars. Published by Universities.®

508 Full-Text Articles 1,820 Authors 27,254 Downloads 59 Institutions

All Articles in Enzymes and Coenzymes

Faceted Search

508 full-text articles. Page 1 of 21.

Mediation Of The Uncoupled Enos Pathway Following Oxidative Stress Using Tetrahydrobiopterin And Nitric Oxide Donor Drugs To Restore Tetrahydrobiopterin Concentration, Brianna Munnich 2021 Olivet Nazarene University

Mediation Of The Uncoupled Enos Pathway Following Oxidative Stress Using Tetrahydrobiopterin And Nitric Oxide Donor Drugs To Restore Tetrahydrobiopterin Concentration, Brianna Munnich

Scholar Week 2016 - present

Presentation Location: Warming House, Olivet Nazarene University

Abstract

The eNOS pathway, found in the endothelium of blood vessels, is a key regulator of nitric oxide levels in the circulatory system. The pathway is controlled through several positive and negative feedback loops [2]. The cofactor tetrahydrobiopterin (BH4) is a major control point in this pathway and under conditions of stress can be reduced into the dihydrobiopterin (BH2) [2,6,7,8,9]. When the reduced form is predominant, the pathway produces reactive oxygen species (ROS) rather than nitric oxide, causing stress and damage to the vessels [6,7,8,9]. In ...


Biotransformation Of Hbe And Other Benzofuran Derivatives, Hannah Trauger 2021 Stephen F Austin State University

Biotransformation Of Hbe And Other Benzofuran Derivatives, Hannah Trauger

Undergraduate Research Conference

No abstract provided.


Toxic Effect Of Crotalus Adamanteus Acidic Phospholipase A2 On Mcf-7 Cell Line, Daniel J. Petra 2021 University of South Dakota

Toxic Effect Of Crotalus Adamanteus Acidic Phospholipase A2 On Mcf-7 Cell Line, Daniel J. Petra

Honors Thesis

We are investigating the effect of Crotalus adamanteus acidic phospholipase A2 on MCF-7 cells using the MTS assay. Understanding these interactions and isolated effects is critical to developing new ways to treat envenomation. By understanding the effects of individual toxins within a whole venom, we are set to better understand the effects of the whole venom and investigate synergistic actions between venom toxins. In this paper, we are quantifying the amount of MCF-7 cell death caused by Crotalus adamanteus phospholipase A2 on MCF-7 using the MTS assay. Analysis of the amount of cells death caused by the phospholipase ...


Non-Apoptotic Enteroblast-Specific Role Of The Initiator Caspase Dronc For Development And Homeostasis Of The Drosophila Intestine, Jillian L. Lindblad, Meghana Tare, Alla Amcheslavsky, Alicia Shields, Andreas Bergmann 2021 University of Massachusetts Medical School

Non-Apoptotic Enteroblast-Specific Role Of The Initiator Caspase Dronc For Development And Homeostasis Of The Drosophila Intestine, Jillian L. Lindblad, Meghana Tare, Alla Amcheslavsky, Alicia Shields, Andreas Bergmann

Open Access Publications by UMMS Authors

The initiator caspase Dronc is the only CARD-domain containing caspase in Drosophila and is essential for apoptosis. Here, we report that homozygous dronc mutant adult animals are short-lived due to the presence of a poorly developed, defective and leaky intestine. Interestingly, this mutant phenotype can be significantly rescued by enteroblast-specific expression of dronc(+) in dronc mutant animals, suggesting that proper Dronc function specifically in enteroblasts, one of four cell types in the intestine, is critical for normal development of the intestine. Furthermore, enteroblast-specific knockdown of dronc in adult intestines triggers hyperplasia and differentiation defects. These enteroblast-specific functions of Dronc do ...


Nad(H) Phosphates Mediate Tetramer Assembly Of Human C-Terminal Binding Protein (Ctbp), Jeffry C. Nichols, Celia A. Schiffer, William E. Royer 2021 University of Massachusetts Medical School

Nad(H) Phosphates Mediate Tetramer Assembly Of Human C-Terminal Binding Protein (Ctbp), Jeffry C. Nichols, Celia A. Schiffer, William E. Royer

University of Massachusetts Medical School Faculty Publications

C-terminal binding proteins (CtBPs) are co-transcriptional factors that play key roles in cell fate. We have previously shown that NAD(H) promotes the assembly of similar tetramers from either human CtBP1 and CtBP2 and that CtBP2 tetramer destabilizing mutants are defective for oncogenic activity. To assist structure-based design efforts for compounds that disrupt CtBP tetramerization, it is essential to understand how NAD(H) triggers tetramer assembly. Here, we investigate the moieties within NAD(H) that are responsible for triggering tetramer formation. Using multi-angle light scattering (MALS) we show that ADP is able to promote tetramer formation of both CtBP1 and ...


Crystal Structure Of Sars-Cov-2 Main Protease In Complex With The Non-Covalent Inhibitor Ml188, Gordon J. Lockbaum, Archie C. Reyes, Jeong Min Lee, Ronak Tilvawala, Ellen A. Nalivaika, Akbar Ali, Nese Kurt Yilmaz, Paul R. Thompson, Celia A. Schiffer 2021 University of Massachusetts Medical School

Crystal Structure Of Sars-Cov-2 Main Protease In Complex With The Non-Covalent Inhibitor Ml188, Gordon J. Lockbaum, Archie C. Reyes, Jeong Min Lee, Ronak Tilvawala, Ellen A. Nalivaika, Akbar Ali, Nese Kurt Yilmaz, Paul R. Thompson, Celia A. Schiffer

COVID-19 Publications by UMMS Authors

Viral proteases are critical enzymes for the maturation of many human pathogenic viruses and thus are key targets for direct acting antivirals (DAAs). The current viral pandemic caused by SARS-CoV-2 is in dire need of DAAs. The Main protease (M(pro)) is the focus of extensive structure-based drug design efforts which are mostly covalent inhibitors targeting the catalytic cysteine. ML188 is a non-covalent inhibitor designed to target SARS-CoV-1 M(pro), and provides an initial scaffold for the creation of effective pan-coronavirus inhibitors. In the current study, we found that ML188 inhibits SARS-CoV-2 M(pro) at 2.5 microM, which is ...


Site-Specific Incorporation Of Citrulline Into Proteins In Mammalian Cells, Santanu Mondal, Shu Wang, Yunan Zheng, Sudeshna Sen, Abhishek Chatterjee, Paul R. Thompson 2021 University of Massachusetts Medical School

Site-Specific Incorporation Of Citrulline Into Proteins In Mammalian Cells, Santanu Mondal, Shu Wang, Yunan Zheng, Sudeshna Sen, Abhishek Chatterjee, Paul R. Thompson

University of Massachusetts Medical School Faculty Publications

Citrullination is a post-translational modification (PTM) of arginine that is crucial for several physiological processes, including gene regulation and neutrophil extracellular trap formation. Despite recent advances, studies of protein citrullination remain challenging due to the difficulty of accessing proteins homogeneously citrullinated at a specific site. Herein, we report a technology that enables the site-specific incorporation of citrulline (Cit) into proteins in mammalian cells. This approach exploits an engineered E. coli-derived leucyl tRNA synthetase-tRNA pair that incorporates a photocaged-citrulline (SM60) into proteins in response to a nonsense codon. Subsequently, SM60 is readily converted to Cit with light in vitro and in ...


Carbon Dots As Artificial Peroxidases For Analytical Applications, Shih-Chun Wei, Yang-Wei Lin, Huan-Tsung Chang 2020 National Taiwan University, Taipei, Taiwan

Carbon Dots As Artificial Peroxidases For Analytical Applications, Shih-Chun Wei, Yang-Wei Lin, Huan-Tsung Chang

Journal of Food and Drug Analysis

Nanozymes have become attractive in analytical and biomedical fields, mainly because of their low cost, long shelf life, and less environmental sensitivity. Particularly, nanozymes formed from nanomaterials having high surface area and rich active sites are interesting since their activities can be tuned through carefully controlling their size, morphology, and surface properties. This review article focuses on preparation of carbon dots (C dots) possessing peroxidase-like activity and their analytical applications. We highlight the important roles of the oxidation states and surface residues of C dots and their nanocomposites with metal, metal oxides, or metal sulfides playing on determining their specificity ...


Viral Packaging Atpases Utilize A Glutamate Switch To Couple Atpase Activity And Dna Translocation [Preprint], Joshua Pajak, Rockney Atz, Brendan J. Hilbert, Marc C. Morais, Brian A. Kelch, Paul Jardine 2020 Duke University

Viral Packaging Atpases Utilize A Glutamate Switch To Couple Atpase Activity And Dna Translocation [Preprint], Joshua Pajak, Rockney Atz, Brendan J. Hilbert, Marc C. Morais, Brian A. Kelch, Paul Jardine

University of Massachusetts Medical School Faculty Publications

Many viruses utilize ringed packaging ATPases to translocate double-stranded DNA into procapsids during replication. A critical step in the mechanochemical cycle of such ATPases is ATP binding, which causes a subunit within the motor to grip DNA tightly. Here, we probe the underlying molecular mechanism by which ATP binding is coupled to DNA gripping and show that a glutamate switch residue found in AAA+ enzymes is central to this coupling in viral packaging ATPases. Using free energy landscapes computed through molecular dynamics simulations, we determined the stable conformational state of the ATPase active site in apo, ATP-bound, and ADP-bound states ...


A 4-Base-Pair Core-Enclosing Helix In Telomerase Rna Is Essential For Activity And For Binding To The Telomerase Reverse Transcriptase Catalytic Protein Subunit, Melissa A. Mefford, Evan P. Hass, David C. Zappulla 2020 Johns Hopkins University

A 4-Base-Pair Core-Enclosing Helix In Telomerase Rna Is Essential For Activity And For Binding To The Telomerase Reverse Transcriptase Catalytic Protein Subunit, Melissa A. Mefford, Evan P. Hass, David C. Zappulla

Open Access Publications by UMMS Authors

The telomerase ribonucleoprotein (RNP) counters the chromosome end replication problem, completing genome replication to prevent cellular senescence in yeast, humans, and most other eukaryotes. The telomerase RNP core enzyme is composed of a dedicated RNA subunit and a reverse transcriptase (telomerase reverse transcriptase [TERT]). Although the majority of the 1,157-nucleotide (nt) Saccharomyces cerevisiae telomerase RNA, TLC1, is rapidly evolving, the central catalytic core is largely conserved, containing the template, template-boundary helix, pseudoknot, and core-enclosing helix (CEH). Here, we show that 4 bp of core-enclosing helix is required for telomerase to be active in vitro and to maintain yeast telomeres ...


Peptidylarginine Deiminase Inhibition Prevents Diabetes Development In Nod Mice, Fernanda M. C. Sodré, Samal Bissenova, Ylke Bruggeman, Ronak Tilvawala, Dana P. Cook, Claire Berthault, Santanu Mondal, Aïsha Callebaut, Sylvaine You, Raphael Scharfmann, Roberto Mallone, Paul R. Thompson, Chantal Mathieu, Mijke Buitinga, Lut Overbergh 2020 KU Leuven

Peptidylarginine Deiminase Inhibition Prevents Diabetes Development In Nod Mice, Fernanda M. C. Sodré, Samal Bissenova, Ylke Bruggeman, Ronak Tilvawala, Dana P. Cook, Claire Berthault, Santanu Mondal, Aïsha Callebaut, Sylvaine You, Raphael Scharfmann, Roberto Mallone, Paul R. Thompson, Chantal Mathieu, Mijke Buitinga, Lut Overbergh

Thompson Lab Publications

Protein citrullination plays a role in several autoimmune diseases. Its involvement in murine and human type 1 diabetes has recently been recognized through the discovery of antibodies and T-cell reactivity against citrullinated peptides. In the current study, we demonstrate that systemic inhibition of peptidylarginine deiminases (PADs), the enzymes mediating citrullination, through BB-Cl-amidine treatment, prevents diabetes development in NOD mice. This prevention was associated with reduced levels of citrullination in the pancreas, decreased circulating autoantibody titers against citrullinated GRP78 and reduced spontaneous NETosis of bone marrow-derived neutrophils. Moreover, BB-Cl-amidine treatment induced a shift from Th1 to Th2 cytokines in the serum ...


The Tec Kinase Itk Differentially Optimizes Nfat, Nf-Κb, And Mapk Signaling During Early T Cell Activation To Regulate Graded Gene Induction [Preprint], Michael P. Gallagher, James M. Conley, Pranitha Vangala, Andrea Reboldi, Manuel Garber, Leslie J. Berg 2020 University of Massachusetts Medical School

The Tec Kinase Itk Differentially Optimizes Nfat, Nf-Κb, And Mapk Signaling During Early T Cell Activation To Regulate Graded Gene Induction [Preprint], Michael P. Gallagher, James M. Conley, Pranitha Vangala, Andrea Reboldi, Manuel Garber, Leslie J. Berg

University of Massachusetts Medical School Faculty Publications

The strength of peptide:MHC interactions with the T cell receptor (TCR) is correlated with the time to first cell division, the relative scale of the effector cell response, and the graded expression of activation-associated proteins like IRF4. To regulate T cell activation programming, the TCR and the TCR proximal kinase ITK simultaneously trigger many biochemically separate TCR signaling cascades. T cells lacking ITK exhibit selective impairments in effector T cell responses after activation, but under the strongest signaling conditions ITK activity is dispensable. To gain insight into whether TCR signal strength and ITK activity tune observed graded gene expression ...


Coevolution, Dynamics And Allostery Conspire In Shaping Cooperative Binding And Signal Transmission Of The Sars-Cov-2 Spike Protein With Human Angiotensin-Converting Enzyme 2, Gennady M. Verkhivker 2020 Chapman University

Coevolution, Dynamics And Allostery Conspire In Shaping Cooperative Binding And Signal Transmission Of The Sars-Cov-2 Spike Protein With Human Angiotensin-Converting Enzyme 2, Gennady M. Verkhivker

Mathematics, Physics, and Computer Science Faculty Articles and Research

Binding to the host receptor is a critical initial step for the coronavirus SARS-CoV-2 spike protein to enter into target cells and trigger virus transmission. A detailed dynamic and energetic view of the binding mechanisms underlying virus entry is not fully understood and the consensus around the molecular origins behind binding preferences of SARS-CoV-2 for binding with the angiotensin-converting enzyme 2 (ACE2) host receptor is yet to be established. In this work, we performed a comprehensive computational investigation in which sequence analysis and modeling of coevolutionary networks are combined with atomistic molecular simulations and comparative binding free energy analysis of ...


Ampa Receptor Surface Expression Is Regulated By S-Nitrosylation Of Thorase And Transnitrosylation Of Nsf, George K. E. Umanah, Mehdi Ghasemi, Valina L. Dawson 2020 Johns Hopkins University

Ampa Receptor Surface Expression Is Regulated By S-Nitrosylation Of Thorase And Transnitrosylation Of Nsf, George K. E. Umanah, Mehdi Ghasemi, Valina L. Dawson

Open Access Publications by UMMS Authors

The regulation of alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptor (AMPAR) trafficking affects multiple brain functions, such as learning and memory. We have previously shown that Thorase plays an important role in the internalization of AMPARs from the synaptic membrane. Here, we show that N-methyl-d-aspartate receptor (NMDAR) activation leads to increased S-nitrosylation of Thorase and N-ethylmaleimide-sensitive factor (NSF). S-nitrosylation of Thorase stabilizes Thorase-AMPAR complexes and enhances the internalization of AMPAR and interaction with protein-interacting C kinase 1 (PICK1). S-nitrosylated NSF is dependent on the S-nitrosylation of Thorase via trans-nitrosylation, which modulates the surface insertion of AMPARs. In the presence of the S-nitrosylation-deficient C137L Thorase ...


Atf-4 And Hydrogen Sulfide Signalling Mediate Longevity From Inhibition Of Translation Or Mtorc1 [Preprint], Cyril Statzer, Pengpeng Liu, Cole M. Haynes, T. Keith Blackwell, Collin Y. Ewald 2020 Swiss Federal Institute of Technology in Zurich

Atf-4 And Hydrogen Sulfide Signalling Mediate Longevity From Inhibition Of Translation Or Mtorc1 [Preprint], Cyril Statzer, Pengpeng Liu, Cole M. Haynes, T. Keith Blackwell, Collin Y. Ewald

University of Massachusetts Medical School Faculty Publications

Inhibition of mTORC1 (mechanistic target of rapamycin 1) slows ageing, but mTORC1 supports fundamental processes that include protein synthesis, making it critical to elucidate how mTORC1 inhibition increases lifespan. Under stress conditions, the integrated stress response (ISR) globally suppresses protein synthesis, resulting in preferential translation of the transcription factor ATF-4. Here we show in C. elegans that the ATF-4 transcription program promotes longevity and that ATF-4 upregulation mediates lifespan extension from mTORC1 inhibition. ATF-4 activates canonical anti-ageing mechanisms but also increases expression of transsulfuration enzymes to promote hydrogen sulfide (H2S) production. ATF-4-induced H2S production mediates longevity ...


A Conserved Myotubularin-Related Phosphatase Regulates Autophagy By Maintaining Autophagic Flux, Elizabeth A. Allen, Clelia Amato, Tina M. Fortier, Panagiotis D. Velentzas, Will Wood, Eric H. Baehrecke 2020 University of Massachusetts Medical School

A Conserved Myotubularin-Related Phosphatase Regulates Autophagy By Maintaining Autophagic Flux, Elizabeth A. Allen, Clelia Amato, Tina M. Fortier, Panagiotis D. Velentzas, Will Wood, Eric H. Baehrecke

Open Access Publications by UMMS Authors

Macroautophagy (autophagy) targets cytoplasmic cargoes to the lysosome for degradation. Like all vesicle trafficking, autophagy relies on phosphoinositide identity, concentration, and localization to execute multiple steps in this catabolic process. Here, we screen for phosphoinositide phosphatases that influence autophagy in Drosophila and identify CG3530. CG3530 is homologous to the human MTMR6 subfamily of myotubularin-related 3-phosphatases, and therefore, we named it dMtmr6. dMtmr6, which is required for development and viability in Drosophila, functions as a regulator of autophagic flux in multiple Drosophila cell types. The MTMR6 family member MTMR8 has a similar function in autophagy of higher animal cells. Decreased dMtmr6 ...


Pad2 Dysregulation And Abnormal Protein Citrullination In Als Disease Models, Issa Yusuf, Tao Qiao, Ronak Tilvawala, Paul R. Thompson, Zuoshang Xu 2020 University of Massachusetts Medical School

Pad2 Dysregulation And Abnormal Protein Citrullination In Als Disease Models, Issa Yusuf, Tao Qiao, Ronak Tilvawala, Paul R. Thompson, Zuoshang Xu

University of Massachusetts Medical School Publications

Amyotrophic lateral sclerosis (ALS) is a deadly neurodegenerative disease characterized by loss of motor neurons, paralysis and eventual death. The mechanism of ALS is still incompletely understood, and the disease is to date without an effective remedy. Protein arginine deiminase 2 (PAD2) converts peptidyl-Arginine into peptidyl-Citrulline, a post-translational modification referred to as citrullination. Aberrant expression of PAD2 and protein citrullination are increased in several neurodegenerative conditions. Whether this increase is involved in ALS is unknown. In this study, we investigated PAD2 and protein citrullination in two genetic mouse models of ALS expressing human mutant SOD1G93A and PFN1C71G, respectively ...


Peptidylarginine Deiminase 2 Has Potential As Both A Biomarker And Therapeutic Target Of Sepsis, Yuzi Tian, Santanu Mondal, Paul R. Thompson, Yongqing Li 2020 Central South University

Peptidylarginine Deiminase 2 Has Potential As Both A Biomarker And Therapeutic Target Of Sepsis, Yuzi Tian, Santanu Mondal, Paul R. Thompson, Yongqing Li

Open Access Publications by UMMS Authors

Peptidylarginine deiminases (PADs) are a family of calcium-dependent enzymes that are involved in a variety of human disorders, including cancer and autoimmune diseases. Although targeting PAD4 has shown no benefit in sepsis, the role of PAD2 remains unknown. Here, we report that PAD2 is engaged in sepsis and sepsis-induced acute lung injury in both human patients and mice. Pad2-/- or selective inhibition of PAD2 by a small molecule inhibitor increased survival and improved overall outcomes in mouse models of sepsis. Pad2 deficiency decreased neutrophil extracellular trap (NET) formation. Importantly, Pad2 deficiency inhibited Caspase-11-dependent pyroptosis in vivo and in vitro. Suppression ...


Flexible Usage And Interconnectivity Of Diverse Cell Death Pathways Protect Against Intracellular Infection, Marcel Doerflinger, Milton Pereira, Andreas Strasser, Sammy Bedoui, Marco J. Herold 2020 University of Melbourne

Flexible Usage And Interconnectivity Of Diverse Cell Death Pathways Protect Against Intracellular Infection, Marcel Doerflinger, Milton Pereira, Andreas Strasser, Sammy Bedoui, Marco J. Herold

Open Access Publications by UMMS Authors

Programmed cell death contributes to host defense against pathogens. To investigate the relative importance of pyroptosis, necroptosis, and apoptosis during Salmonella infection, we infected mice and macrophages deficient for diverse combinations of caspases-1, -11, -12, and -8 and receptor interacting serine/threonine kinase 3 (RIPK3). Loss of pyroptosis, caspase-8-driven apoptosis, or necroptosis had minor impact on Salmonella control. However, combined deficiency of these cell death pathways caused loss of bacterial control in mice and their macrophages, demonstrating that host defense can employ varying components of several cell death pathways to limit intracellular infections. This flexible use of distinct cell death ...


Caspase-8 Mediates Inflammation And Disease In Rodent Malaria, Larissa M. N. Pereira, Patricia Aparecida Assis, Natalia M. de Araujo, Danielle Fernandes Durso, Caroline Junqueira, Marco Antonio Ataide, Dhelio B. Pereira, Egil Lien, Katherine A. Fitzgerald, Dario S. Zamboni, Douglas T. Golenbock, Ricardo T. Gazzinelli 2020 University of Massachusetts Medical School

Caspase-8 Mediates Inflammation And Disease In Rodent Malaria, Larissa M. N. Pereira, Patricia Aparecida Assis, Natalia M. De Araujo, Danielle Fernandes Durso, Caroline Junqueira, Marco Antonio Ataide, Dhelio B. Pereira, Egil Lien, Katherine A. Fitzgerald, Dario S. Zamboni, Douglas T. Golenbock, Ricardo T. Gazzinelli

Open Access Publications by UMMS Authors

Earlier studies indicate that either the canonical or non-canonical pathways of inflammasome activation have a limited role on malaria pathogenesis. Here, we report that caspase-8 is a central mediator of systemic inflammation, septic shock in the Plasmodium chabaudi-infected mice and the P. berghei-induced experimental cerebral malaria (ECM). Importantly, our results indicate that the combined deficiencies of caspases-8/1/11 or caspase-8/gasdermin-D (GSDM-D) renders mice impaired to produce both TNFalpha and IL-1beta and highly resistant to lethality in these models, disclosing a complementary, but independent role of caspase-8 and caspases-1/11/GSDM-D in the pathogenesis of malaria. Further, we find ...


Digital Commons powered by bepress