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Raj S.B.,University of Iowa | Raj S.B.,Lawson State Community College | Ramaswamy S.,University of Iowa | Ramaswamy S.,Institute for Stem Cell Biology and Regenerative Medicine InStem | Plapp B.V.,University of Iowa

Yeast (Saccharomyces cerevisiae) alcohol dehydrogenase I (ADH1) is the constitutive enzyme that reduces acetaldehyde to ethanol during the fermentation of glucose. ADH1 is a homotetramer of subunits with 347 amino acid residues. A structure for ADH1 was determined by X-ray crystallography at 2.4 Å resolution. The asymmetric unit contains four different subunits, arranged as similar dimers named AB and CD. The unit cell contains two different tetramers made up of "back-to-back" dimers, AB:AB and CD:CD. The A and C subunits in each dimer are structurally similar, with a closed conformation, bound coenzyme, and the oxygen of 2,2,2-trifluoroethanol ligated to the catalytic zinc in the classical tetrahedral coordination with Cys-43, Cys-153, and His-66. In contrast, the B and D subunits have an open conformation with no bound coenzyme, and the catalytic zinc has an alternative, inverted coordination with Cys-43, Cys-153, His-66, and the carboxylate of Glu-67. The asymmetry in the dimeric subunits of the tetramer provides two structures that appear to be relevant for the catalytic mechanism. The alternative coordination of the zinc may represent an intermediate in the mechanism of displacement of the zinc-bound water with alcohol or aldehyde substrates. Substitution of Glu-67 with Gln-67 decreases the catalytic efficiency by 100-fold. Previous studies of structural modeling, evolutionary relationships, substrate specificity, chemical modification, and site-directed mutagenesis are interpreted more fully with the three-dimensional structure. © 2014 American Chemical Society. Source

Eipper-Mains J.E.,University of Connecticut Health Center | Kiraly D.D.,University of Connecticut Health Center | Palakodeti D.,University of Connecticut Health Center | Palakodeti D.,Institute for Stem Cell Biology and Regenerative Medicine InStem | And 3 more authors.

MicroRNAs (miRNAs) are small RNAs that modulate gene expression by binding target mRNAs. The hundreds of miRNAs expressed in the brain are critical for synaptic development and plasticity. Drugs of abuse cause lasting changes in the limbic regions of the brain that process reward, and addiction is viewed as a form of aberrant neuroplasticity. Using next-generation sequencing, we cataloged miRNA expression in the nucleus accumbens and at striatal synapses in control and chronically cocaine-treated mice. We identified cocaine-responsive miRNAs, synaptically enriched and depleted miRNA families, and confirmed cocaine-induced changes in protein expression for several predicted synaptic target genes. The miR-8 family, known for its roles in cancer, is highly enriched and cocaine regulated at striatal synapses, where its members may affect expression of cell adhesion molecules. Synaptically enriched cocaine-regulated miRNAs may contribute to long-lasting drug-induced plasticity through fine-tuning regulatory pathways that modulate the actin cytoskeleton, neurotransmitter metabolism, and peptide hormone processing. Published by Cold Spring Harbor Laboratory Press. Copyright © 2011 RNA Society. Source

Plapp B.V.,University of Iowa | Ramaswamy S.,University of Iowa | Ramaswamy S.,Institute for Stem Cell Biology and Regenerative Medicine InStem

Structures of horse liver alcohol dehydrogenase complexed with NAD + and unreactive substrate analogues, 2,2,2-trifluoroethanol or 2,3,4,5,6-pentafluorobenzyl alcohol, were determined at 100 K at 1.12 or 1.14 Å resolution, providing estimates of atomic positions with overall errors of ∼0.02 Å, the geometry of ligand binding, descriptions of alternative conformations of amino acid residues and waters, and evidence of a strained nicotinamide ring. The four independent subunits from the two homodimeric structures differ only slightly in the peptide backbone conformation. Alternative conformations for amino acid side chains were identified for 50 of the 748 residues in each complex, and Leu-57 and Leu-116 adopt different conformations to accommodate the different alcohols at the active site. Each fluoroalcohol occupies one position, and the fluorines of the alcohols are well-resolved. These structures closely resemble the expected Michaelis complexes with the pro-R hydrogens of the methylene carbons of the alcohols directed toward the re face of C4N of the nicotinamide rings with a C-C distance of 3.40 Å. The oxygens of the alcohols are ligated to the catalytic zinc at a distance expected for a zinc alkoxide (1.96 Å) and participate in a low-barrier hydrogen bond (2.52 Å) with the hydroxyl group of Ser-48 in a proton relay system. As determined by X-ray refinement with no restraints on bond distances and planarity, the nicotinamide rings in the two complexes are slightly puckered (quasi-boat conformation, with torsion angles of 5.9° for C4N and 4.8° for N1N relative to the plane of the other atoms) and have bond distances that are somewhat different compared to those found for NAD(P)+. It appears that the nicotinamide ring is strained toward the transition state on the path to alcohol oxidation. © 2012 American Chemical Society. Source

Lalitha K.,SASTRA University | Muthusamy K.,SASTRA University | Prasad Y.S.,SASTRA University | Vemula P.K.,Institute for Stem Cell Biology and Regenerative Medicine InStem | Nagarajan S.,SASTRA University
Carbohydrate Research

In the last few years, considerable progress has been made in the synthesis of C-glycosides. Despite its challenging chemistry, due to its versatility, C-glycosides play a pivotal role in developing novel materials, surfactants and bioactive molecules. In this review, we present snapshots of various synthetic methodologies developed for C-glycosides in the recent years and the potential application of C-glycosides derived from β-C-glycosidic ketones © 2014 Elsevier Ltd. All rights reserved.. Source

Anand T.,Madurai Kamaraj University | Sivaraman G.,Madurai Kamaraj University | Sivaraman G.,Institute for Stem Cell Biology and Regenerative Medicine InStem | Iniya M.,Madurai Kamaraj University | And 2 more authors.
Analytica Chimica Acta

Chemosensors based on aminobenzohydrazide Schiff bases bearing pyrene/anthracene as fluorophores have been designed and synthesized for F- ion recognition. The addition of fluoride ions to the receptors causes a dramatically observable colour change from pale yellow to brown/red. 1H NMR studies confirm that the F- ion facilitates its recognition by forming hydrogen bond with hydrogens of amide and amine groups. Moreover these sensors have also been successfully applied to detection of fluoride ion in commercial tooth paste solution. © 2015 Elsevier B.V.. Source

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