Nucleic Acids, Nucleotides, and Nucleosides Commons^™

Methyl Transfer By Substrate Signaling From A Knotted Protein Fold, Thomas Christian, Reiko Sakaguchi, Agata P. Perlinska, George Lahoud, Takuhiro Ito, Erika A. Taylor, Shigeyuki Yokoyama, Joanna I. Sulkowska, Ya-Ming Hou

Erika A. Taylor, Ph.D.

Micrornas In Alcoholic Liver Disease, Gyongyi Szabo, Abhishek Satishchandran

Gyongyi Szabo

Alcoholic liver disease (ALD) is characterized by hepatocyte damage, inflammatory cell activation and increased intestinal permeability leading to the clinical manifestations of alcoholic hepatitis. Selected members of the family of microRNAs are affected by alcohol, resulting in an abnormal miRNA profile in the liver and circulation in ALD. Increasing evidence suggests that mRNAs that regulate inflammation, lipid metabolism and promote cancer are affected by excessive alcohol administration in mouse models of ALD. This communication highlights recent findings in miRNA expression and functions as they relate to the pathogenesis of ALD. The cell-specific distribution of miRNAs, as well as the significance …

Introduction To Gene Enrichment Analysis Tools, Rolando Garcia-Milian

Rolando Garcia-Milian

Bioinformatics enrichment tools play an important role in identifying, annotating, and functionally analyzing large list of genes generated by high-throughput technologies (e.g. microarrary, RNA-seq, ChIP-chip). This workshop will provide an overview of the principle, type of enrichments, and the infrastructure of enrichment tools. By using concrete examples, it will also introduce some of the most popular tools for gene enrichment analysis such as DAVID, GSEA, and WebGestalt.

Leica Microscope Gpu Deconvolution Stellaris Fish Dataset #1, George Mcnamara

George McNamara

McNamara 20131101Fri Leica widefield microscope CUDA Deconvolution Stellaris FISH probe cultured cells dataset #1.zip

A text file in the zip archive has experiment details. I am posting this online so that researchers - whether academic or commercial - can evaluate the acquired data, the Bruce and Butte 2013 Optics Express ( http://www.opticsinfobase.org/oe/fulltext.cfm?uri=oe-21-4-4766 ) deconvolution result (note: I may not have used optimal settings), and to compare these deconvolution results to other methods. If anyone generates alternative spatial deconvolution output, such as from: * SVI Huygens * Media Cy AutoQuant * Agard's ER-Decon (Arigovindan 2013 PNAS) * Vicidomini SGP GPU Deconv …

Anopheles Gambiae Purine Nucleoside Phosphorylase: Catalysis, Structure And Inhibition, Erika Taylor, Agnes Rinaldo-Matthis, Lei Li, Mahmoud Ghanem, Keith Hazleton, M. Belen Cassera, Steven Almo, Vern Schramm

Erika A. Taylor, Ph.D.

The purine salvage pathway of Anopheles gambiae, a mosquito that transmits malaria, has been identified in genome searches on the basis of sequence homology with characterized enzymes. Purine nucleoside phosphorylase (PNP) is a target for the development of therapeutic agents in humans and purine auxotrophs, including malarial parasites. The PNP from Anopheles gambiae (AgPNP) was expressed in Escherichia coli and compared to the PNPs from Homo sapiens (HsPNP) and Plasmodium falciparum (PfPNP). AgPNP has kcat values of 54 and 41 s-1 for 2'-deoxyinosine and inosine, its preferred substrates, and 1.0 s-1 for guanosine. However, the chemical step is fast for …

Transition-State Variation In Human, Bovine, And Plasmodium Falciparum Adenosine Deaminases, Minkui Lou, Vipender Singh, Erika Taylor, Vern Schramm

Erika A. Taylor, Ph.D.

Adenosine deaminases (ADAs) from human, bovine, and Plasmodium falciparum sources were analyzed by kinetic isotope effects (KIEs) and shown to have distinct but related transition states. Human adenosine deaminase (HsADA) is present in most mammalian cells and is involved in B- and T-cell development. The ADA from Plasmodium falciparum (PfADA) is essential in this purine auxotroph, and its inhibition is expected to have therapeutic effects for malaria. Therefore, ADA is of continuing interest for inhibitor design. Stable structural mimics of ADA transition states are powerful inhibitors. Here we report the transition-state structures of PfADA, HsADA, and bovine ADA (BtADA) solved …

Acyclic Ribooxacarbenium Ion Mimics As Transition State Analogues Of Human And Malarial Purine Nucleoside Phosphorylases, Erika Taylor, Keith Clinch, Peter Kelly, Lei Li, Gary Evans, Peter Tyler, Vern Schramm

Erika A. Taylor, Ph.D.

Transition state analogues of PNP, the Immucillins and DADMe-Immucillins, were designed to match transition state features of bovine and human PNPs, respectively. A third generation of inhibitors has been designed that contain an acyclic iminoalcohol to replace the cyclic mimic of the ribooxacarbenium ion at the transition states of PNPs. The best third generation inhibitor is equivalent to the best inhibitors found in the previous transition state analogues.

Synthesis Of 5‘-Methylthio Coformycins:  Specific Inhibitors For Malarial Adenosine Deaminase, Peter Tyler, Erika Taylor, Richard Froehlich, Vern Schramm

Erika A. Taylor, Ph.D.

Transition state theory suggests that enzymatic rate acceleration (kcat/knon) is related to the stabilization of the transition state for a given reaction. Chemically stable analogues of a transition state complex are predicted to convert catalytic energy into binding energy. Because transition state stabilization is a function of catalytic efficiency, differences in substrate specificity can be exploited in the design of tight-binding transition state analogue inhibitors. Coformycin and 2‘-deoxycoformycin are natural product transition state analogue inhibitors of adenosine deaminases (ADAs). These compounds mimic the tetrahedral geometry of the ADA transition state and bind with picomolar dissociation constants to enzymes from bovine, …

Neighboring Group Participation In The Transition State Of Human Purine Nucleoside Phosphorylase, Andrew Murkin, Matthew Birck, Agnes Rinaldo-Matthis, Wuxian Shi, Erika Taylor, Steven Almo, Vern Schramm

Erika A. Taylor, Ph.D.

No abstract provided.