Medical Biochemistry Commons™
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Recent Articles in Medical Biochemistry
Amalgamation Of Nucleosides And Amino Acids In Antibiotic Biosynthesis, Sandra H. Barnard
University of Kentucky
Amalgamation Of Nucleosides And Amino Acids In Antibiotic Biosynthesis, Sandra H. Barnard
Theses and Dissertations--Pharmacy
The rapid increase in antibiotic resistance demands the identification of novel antibiotics with novel targets. One potential antibacterial target is the biosynthesis of peptidoglycan cell wall, which is both ubiquitous and necessary for bacterial survival. Both the caprazamycin-related compounds A-90289 and muraminomicin, as well as the capuramycin-related compounds A-503083 and A-102395 are potent inhibitors of the translocase I enzyme, one of the key enzymes required for cell wall biosynthesis. The caprazamycin-related compounds contain a core nonproteinogen b-hydroxy-a-amino acid referred to as 5’-C-glycyluridine (GlyU). Residing within the biosynthetic gene clusters of the aforementioned compounds is a shared open reading ...
Heterogeneity In Platelet Exocytosis, Deepa Jonnalagadda
University of Kentucky
Heterogeneity In Platelet Exocytosis, Deepa Jonnalagadda
Theses and Dissertations--Molecular and Cellular Biochemistry
Platelet exocytosis is essential for hemostasis and for many of its sequelae. Platelets release numerous bioactive molecules stored in their granules enabling them to exert a wide range of effects on the vascular microenvironment. Are these granule cargo released thematically in a context-specific pattern or via a stochastic, kinetically-controlled process? My work describes platelet exocytosis using a systematic examination of platelet secretion kinetics. Platelets were stimulated for increasing times with different agonists (i.e. thrombin, PAR1-agonist, PAR4-agonist, and convulxin) and micro-ELISA arrays were used to quantify the release of 28 distinct α-granule cargo molecules. Agonist potency directly correlated with the ...
Possible Steps Of Complete Disassembly Of Post-Termination Complex By Yeast Eef3 Deduced From Inhibition By Translocation Inhibitors., Shinya Kurata, Ben Shen, Jun O Liu, Nono Takeuchi, Akira Kaji, Hideko Kaji
Thomas Jefferson University
Possible Steps Of Complete Disassembly Of Post-Termination Complex By Yeast Eef3 Deduced From Inhibition By Translocation Inhibitors., Shinya Kurata, Ben Shen, Jun O Liu, Nono Takeuchi, Akira Kaji, Hideko Kaji
Department of Biochemistry and Molecular Biology Faculty Papers
Ribosomes, after one round of translation, must be recycled so that the next round of translation can occur. Complete disassembly of post-termination ribosomal complex (PoTC) in yeast for the recycling consists of three reactions: release of tRNA, release of mRNA and splitting of ribosomes, catalyzed by eukaryotic elongation factor 3 (eEF3) and ATP. Here, we show that translocation inhibitors cycloheximide and lactimidomycin inhibited all three reactions. Cycloheximide is a non-competitive inhibitor of both eEF3 and ATP. The inhibition was observed regardless of the way PoTC was prepared with either release factors or puromycin. Paromomycin not only inhibited all three reactions ...
Targeting Astrocytes Ameliorates Neurologic Changes In A Mouse Model Of Alzheimer's Disease, Jennifer L. Furman, Diana M. Sama, John C. Gant, Tina L. Beckett, M. Paul Murphy, Adam D. Bachstetter, Linda J. Van Eldik, Christopher M. Norris
University of Kentucky
Targeting Astrocytes Ameliorates Neurologic Changes In A Mouse Model Of Alzheimer's Disease, Jennifer L. Furman, Diana M. Sama, John C. Gant, Tina L. Beckett, M. Paul Murphy, Adam D. Bachstetter, Linda J. Van Eldik, Christopher M. Norris
Molecular and Biomedical Pharmacology Faculty Publications
Astrocytes are the most abundant cell type in the brain and play a critical role in maintaining healthy nervous tissue. In Alzheimer's disease (AD) and most other neurodegenerative disorders, many astrocytes convert to a chronically "activated" phenotype characterized by morphologic and biochemical changes that appear to compromise protective properties and/or promote harmful neuroinflammatory processes. Activated astrocytes emerge early in the course of AD and become increasingly prominent as clinical and pathological symptoms progress, but few studies have tested the potential of astrocyte-targeted therapeutics in an intact animal model of AD. Here, we used adeno-associated virus (AAV) vectors containing ...
Possible Steps Of Complete Disassembly Of Post-Termination Complex By Yeast Eef3 Deduced From Inhibition By Translocation Inhibitors., Shinya Kurata, Ben Shen, Jun O Liu, Nono Takeuchi, Akira Kaji, Hideko Kaji
Thomas Jefferson University
Possible Steps Of Complete Disassembly Of Post-Termination Complex By Yeast Eef3 Deduced From Inhibition By Translocation Inhibitors., Shinya Kurata, Ben Shen, Jun O Liu, Nono Takeuchi, Akira Kaji, Hideko Kaji
Department of Biochemistry and Molecular Biology Faculty Papers
Ribosomes, after one round of translation, must be recycled so that the next round of translation can occur. Complete disassembly of post-termination ribosomal complex (PoTC) in yeast for the recycling consists of three reactions: release of tRNA, release of mRNA and splitting of ribosomes, catalyzed by eukaryotic elongation factor 3 (eEF3) and ATP. Here, we show that translocation inhibitors cycloheximide and lactimidomycin inhibited all three reactions. Cycloheximide is a non-competitive inhibitor of both eEF3 and ATP. The inhibition was observed regardless of the way PoTC was prepared with either release factors or puromycin. Paromomycin not only inhibited all three reactions ...
Characterization Of Copn (Cpn0324) The Putative Type Iii Secretion System Plug Protein Of Chlamydia Pneumoniae, Tiffany L. Leighton
McMaster University
Characterization Of Copn (Cpn0324) The Putative Type Iii Secretion System Plug Protein Of Chlamydia Pneumoniae, Tiffany L. Leighton
Open Access Dissertations and Theses
Chlamydia pneumoniae is a Gram-negative, intracellular bacterium which utilizes a type III secretion system for virulence. This system injects virulence associated proteins into a host cell and ultimately hijacks host intracellular machinery required for the bacteria to propagate and reproduce. Chlamydia outer protein N or CopN (Cpn0324), is a member of a family of proteins found in pathogenic bacteria, which inhibits premature secretion of effector proteins by plugging the base of the injectisome. The lack of a genetic system to manipulate the bacteria hampers the identification of proteins within the T3S field. The work presented in this thesis establishes the ...
Fusing The C-Terminal Tridecapeptide Of Hirudin To Α1-Proteinase Inhibitor M358r Accelerates Its Rate Of Thrombin Inhibition, Leigh Ann C. Roddick
McMaster University
Fusing The C-Terminal Tridecapeptide Of Hirudin To Α1-Proteinase Inhibitor M358r Accelerates Its Rate Of Thrombin Inhibition, Leigh Ann C. Roddick
Open Access Dissertations and Theses
The serpin α-1 proteinase inhibitor (API) normally only impacts the coagulation cascade through its ability to inactivate factor XIa. However, the point mutation (Met to Arg) at position 358 results in a potent thrombin inhibitor, API M358R. This mutation also enhances this serpin’s ability to inhibit the anticoagulant protein, activated protein C (APC) and hence this property limits its therapeutic potential. As a result, various modifications to this protein have been engineered in order to enhance its specificity towards thrombin. Previously, the Heparin Cofactor II (HCII) N-terminal tail, HCII 1-75, which binds exosite 1 of thrombin, was tethered to ...
The Cross Talk Between Trkb And Nmda Receptors Through Rasgrf1, Asghar Talebian
Western University
The Cross Talk Between Trkb And Nmda Receptors Through Rasgrf1, Asghar Talebian
Electronic Thesis and Dissertation Repository
Introduction: Brain-derived neurotrophic factor (BDNF) facilitates neuronal differentiation by activation of the TrkB receptor-tyrosine-kinase. BDNF/TrkB also modulates the activity of the excitatory N-methyl-D-aspartate neurotransmitter receptor (NMDAR), thereby also regulating neural plasticity and LTP/LTD, two forms of synaptic plasticity that contribute to the storage of information inside the brain. How TrkB cross-talks to modulate NMDAR function is not known, although our working model involves the RasGrf1 signaling molecule, a nucleotide exchange factor for Ras/Rac-GTPases, which interacts with both receptors. In response to TrkB activation, Ras-Grf1 is tyrosine phosphorylated and mediates neurite outgrowth in PC12 cells. RasGrf1 also ...
Global Cellular Regulation Including Cardiac Function By Post-Translational Protein Arginylation., Hideko Kaji, Akira Kaji
Thomas Jefferson University
Global Cellular Regulation Including Cardiac Function By Post-Translational Protein Arginylation., Hideko Kaji, Akira Kaji
Department of Biochemistry and Molecular Biology Faculty Papers
In this issue a very significant contribution to cardiology describing critical roles of ATE1 appears by Kurosaka et al. [1]. In view of this paper, as the discoverers of ATE1, we have been asked to contribute an article (editorial) regarding ATE1 (enzyme which transfers arginine from arginyl tRNA to protein acceptors). This short article consists of three sections: 1) a historical anecdote describing how ATE1 was discovered; 2) its possible role in aging and cellular transformation, and most importantly; 3) its role in the development and maintenance of cardiac activity. The last section has direct bearing to the Kurosaka et ...
The New Role Of Proprotein Convertase Subtilisin/Kexin Type 9: A Connection Of Proprotein Convertase Subtilisin/Kexin Type 9, Apolipoprotein B, And Autophagy, Hua Sun
Texas Medical Center Library
The New Role Of Proprotein Convertase Subtilisin/Kexin Type 9: A Connection Of Proprotein Convertase Subtilisin/Kexin Type 9, Apolipoprotein B, And Autophagy, Hua Sun
UT GSBS Dissertations and Theses (Open Access)
Plasma low-density lipoprotein (LDL) levels are positively correlated with the incidence of coronary artery disease. In the circulation, the plasma LDL clearance is mainly achieved by the uptake via LDL receptor (LDLR). Proprotein convertase subtilisin/kexin type 9 (PCSK9) is a newly discovered gene, playing an important role in LDL metabolism. Gain-of-function mutations of PCSK9 lead to hypercholesterolemia and loss-of-function mutations of PCSK9 are associated with decrease of LDL cholesterol. The effects of PCSK9 on cholesterol levels are the consequence of a strong interaction between the catalytic domain of PCSK9 and epidermal growth factor-like repeat A (EGF-A) domain of LDLR ...
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Combating Intrinsic Antibiotic Resistance In Gram-Negative Bacteria, Patricia Taylor
Development Of Novel Ahr Antagonists, Hyosung Lee
Heterogeneity In Platelet Exocytosis, Deepa Jonnalagadda
Blood Cell Lineage Chart, David Kendall,
Cell-Matrix Adhesion In Muscle Development And Disease
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