Open Access. Powered by Scholars. Published by Universities.®
Biochemistry, Biophysics, and Structural Biology Commons™
Open Access. Powered by Scholars. Published by Universities.®
- Institution
- Keyword
- Publication
- Publication Type
- File Type
Articles 1 - 9 of 9
Full-Text Articles in Biochemistry, Biophysics, and Structural Biology
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
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 …
Phenylalanyl-Trna Synthetase Editing Defects Result In Efficient Mistranslation Of Phenylalanine Codons As Tyrosine, Jiqiang Ling, Srujana S. Yadavalli, Michael Ibba
Phenylalanyl-Trna Synthetase Editing Defects Result In Efficient Mistranslation Of Phenylalanine Codons As Tyrosine, Jiqiang Ling, Srujana S. Yadavalli, Michael Ibba
Biology, Chemistry, and Environmental Sciences Faculty Articles and Research
Translational quality control is monitored at several steps, including substrate selection by aminoacyl-tRNA synthetases (aaRSs), and discrimination of aminoacyl-tRNAs by elongation factor Tu (EF-Tu) and the ribosome. Phenylalanyl-tRNA synthetase (PheRS) misactivates Tyr but is able to correct the mistake using a proofreading activity named editing. Previously we found that overproduction of editing-defective PheRS resulted in Tyr incorporation at Phe-encoded positions in vivo , although the misreading efficiency could not be estimated. This raised the question as to whether or not EF-Tu and the ribosome provide further proofreading mechanisms to prevent mistranslation of Phe codons by Tyr. Here we show that, …
An Aminoacyl-Trna Synthetase: Elongation Factor Complex For Substrate Channeling In Archaeal Translation, Corinne D. Hausmann, Mette Praetorius-Ibba, Michael Ibba
An Aminoacyl-Trna Synthetase: Elongation Factor Complex For Substrate Channeling In Archaeal Translation, Corinne D. Hausmann, Mette Praetorius-Ibba, Michael Ibba
Biology, Chemistry, and Environmental Sciences Faculty Articles and Research
Translation requires the specific attachment of amino acids to tRNAs by aminoacyl-tRNA synthetases (aaRSs) and the subsequent delivery of aminoacyl-tRNAs to the ribosome by elongation factor 1 alpha (EF-1α). Interactions between EF-1α and various aaRSs have been described in eukaryotes, but the role of these complexes remains unclear. To investigate possible interactions between EF-1α and other cellular components, a yeast two-hybrid screen was performed for the archaeon Methanothermobacter thermautotrophicus. EF-1α was found to form a stable complex with leucyl-tRNA synthetase (LeuRS; KD = 0.7 μ M). Complex formation had little effect on EF-1α activity, but increased the kcat …
Transition-State Variation In Human, Bovine, And Plasmodium Falciparum Adenosine Deaminases, Minkui Lou, Vipender Singh, Erika Taylor, Vern Schramm
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 …
Biochemical Characteristics Of Inconsistent Free T₄ Assays, Kristofer S. Fritz
Biochemical Characteristics Of Inconsistent Free T₄ Assays, Kristofer S. Fritz
Loma Linda University Electronic Theses, Dissertations & Projects
Serum levels of free thyroxine (T4) are helpful in the clinical evaluation of patients who are suspected of having thyroid disease, since free T4 (unbound) is known to closely relate to hyper, eu and hypothyroidism. There are documented inconsistencies among commercially available direct free thyroxine immunoassays. The biochemical basis for these inconsistencies is not understood and has not been characterized. Direct free T4 measurements have been linked to both T4-binding serum protein concentrations and protein-bound T4 concentrations. A free T4 reference method using direct equilibrium dialysis radioimmunoassay has been well characterized. New …
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
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
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
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.
Dna Multiplex Hybridization On Microarrays And Thermodynamic Stability In Solution: A Direct Comparison, Daniel J. Fish, M. Todd Horne, Greg P. Brewood, Jim P. Goodarzi, Saba Alemayehu, Ashwini Bhandiwad, Robert P. Searles, Albert S. Benight
Dna Multiplex Hybridization On Microarrays And Thermodynamic Stability In Solution: A Direct Comparison, Daniel J. Fish, M. Todd Horne, Greg P. Brewood, Jim P. Goodarzi, Saba Alemayehu, Ashwini Bhandiwad, Robert P. Searles, Albert S. Benight
Chemistry Faculty Publications and Presentations
Hybridization intensities of 30 distinct short duplex DNAs measured on spotted microarrays, were directly compared with thermodynamic stabilities measured in solution. DNA sequences were designed to promote formation of perfect match, or hybrid duplexes containing tandem mismatches. Thermodynamic parameters DeltaH degrees , DeltaS degrees and DeltaG degrees of melting transitions in solution were evaluated directly using differential scanning calorimetry. Quantitative comparison with results from 63 multiplex microarray hybridization experiments provided a linear relationship for perfect match and most mismatch duplexes. Examination of outliers suggests that both duplex length and relative position of tandem mismatches could be important factors contributing to …