A5047422822- RNA and protein synthesis mechanisms
- RNA modifications and cancer
- RNA Research and Splicing
- Genomics and Phylogenetic Studies
- Bacterial Genetics and Biotechnology
- RNA regulation and disease
- Bacteriophages and microbial interactions
- Biochemical and Molecular Research
- Hemoglobin structure and function
- Chemical Synthesis and Analysis
- Cytomegalovirus and herpesvirus research
- Microbial infections and disease research
- Porphyrin Metabolism and Disorders
- Metal-Catalyzed Oxygenation Mechanisms
- Adenosine and Purinergic Signaling
- COVID-19 epidemiological studies
- CRISPR and Genetic Engineering
- SARS-CoV-2 detection and testing
- Advanced biosensing and bioanalysis techniques
- DNA and Nucleic Acid Chemistry
- Metabolomics and Mass Spectrometry Studies
- Machine Learning in Bioinformatics
- Pharmacogenetics and Drug Metabolism
- SARS-CoV-2 and COVID-19 Research
- Enzyme Structure and Function
University of Illinois Urbana-Champaign
2012-2022
University of Illinois System
2017
Cubist Pharmaceuticals (United States)
1998-2014
Institute of Molecular Biology and Biophysics
2011-2013
Chancellor University
1991-2012
Stahl-Zentrum (Germany)
2009
University of Houston
1997-2007
European Molecular Biology Laboratory
2007
Institute of Molecular Biology and Genetics
2007
Shanghai Jiao Tong University
2007
Aminoacyl-transfer RNA (tRNA) synthetases, which catalyze the attachment of correct amino acid to its corresponding tRNA during translation genetic code, are proven antimicrobial drug targets. We show that broad-spectrum antifungal 5-fluoro-1,3-dihydro-1-hydroxy-2,1-benzoxaborole (AN2690), in development for treatment onychomycosis, inhibits yeast cytoplasmic leucyl-tRNA synthetase by formation a stable tRNA(Leu)-AN2690 adduct editing site enzyme. Adduct is mediated through boron atom AN2690...
ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXTA conserved residue of cytochrome P-450 is involved in heme-oxygen stability and activationSusan A. Martinis, William M. Atkins, Patrick S. Stayton, Stephen G. SligarCite this: J. Am. Chem. Soc. 1989, 111, 26, 9252–9253Publication Date (Print):December 1, 1989Publication History Published online1 May 2002Published inissue 1 December 1989https://pubs.acs.org/doi/10.1021/ja00208a031https://doi.org/10.1021/ja00208a031research-articleACS...
ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXTCrystal structure of the cytochrome P-450CAM active site mutant Thr252AlaReetta Raag, Susan A. Martinis, Stephen G. Sligar, and Thomas L. PoulosCite this: Biochemistry 1991, 30, 48, 11420–11429Publication Date (Print):December 3, 1991Publication History Published online1 May 2002Published inissue 3 December 1991https://pubs.acs.org/doi/10.1021/bi00112a008https://doi.org/10.1021/bi00112a008research-articleACS PublicationsRequest reuse...
ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXTAlteration of sperm whale myoglobin heme axial ligation by site-directed mutagenesisKaren D. Egeberg, Barry A. Springer, Susan Martinis, Stephen G. Sligar, Dimitrios Morikis, and Paul M. ChampionCite this: Biochemistry 1990, 29, 42, 9783–9791Publication Date (Print):October 1, 1990Publication History Published online1 May 2002Published inissue 1 October...
Mycoplasma parasites escape host immune responses via mechanisms that depend on remarkable phenotypic plasticity. Identification of these is great current interest. The aminoacyl-tRNA synthetases (AARSs) attach amino acids to their cognate tRNAs, but occasionally make errors substitute closely similar acids. AARS editing pathways clear avoid mistranslation during protein synthesis. We show here AARSs in have point mutations and deletions respective domains. deleterious effect was confirmed...
Leucyl-tRNA synthetase (LRS) is known to function as leucine sensor in the mammalian target of rapamycin complex 1 (mTORC1) pathway. However, pathophysiological significance its activity not well understood. Here, we demonstrate that for mTORC1 activation LRS can be decoupled from catalytic activity. We identified compounds inhibit leucine-dependent pathway by specifically inhibiting GTPase activating LRS, while affecting For further analysis, selected one compound, BC-LI-0186, which binds...
Aminoacyl-tRNA synthetases ensure the fidelity of protein synthesis by accurately selecting and activating cognate amino acids for aminoacylation correct tRNA. Some tRNA have evolved an editing active site that is separate from acid activation providing two steps or "sieves" selection. These sieves rely on different strategies recognition to significantly enhance accuracy aminoacylation. We performed alanine scanning mutagenesis in a conserved threonine-rich region Escherichia coli...
Cytochrome P450cam was subjected to high pressures of 2.2 kbar, converting the enzyme its inactive form, P420cam. The resultant protein characterized by electron paramagnetic resonance, magnetic circular dichroism, and electronic absorption spectroscopy. A range exogenous ligands has been employed probe coordination structure results suggest that conversion P420cam involves a conformational change which restricts substrate binding site and/or alters ligand access channel. reduction potential...
High-resolution resonance Raman spectra of the ferric, ferrous, and carbonmonoxy (CO)-bound forms wild-type Escherichia coli-expressed Pseudomonas putida cytochrome P450cam its P420 form are reported. The ferric ferrous species P450 have been studied in both presence absence excess camphor substrate. In camphor-bound, (mos), E. is found to be spectroscopically indistinguishable from native material. Although substrate binding known displace water molecules heme pocket, altering coordination...
Mistranslation is toxic to bacterial and mammalian cells can lead neurodegeneration in the mouse. caused by attachment of wrong amino acid a specific tRNA. Many aminoacyl-tRNA synthetases have an editing activity that deacylates mischarged before capture elongation factor transport ribosome. For class I tRNA synthetases, encoded CP1 domain, which distinct from active site for aminoacylation. What not clear whether enzymes also separable CP1. A point mutation leucyl-tRNA synthetase...
RNA hairpin helices whose sequences are based on the acceptor stems of alanine and histidine tRNAs specifically aminoacylated with their cognate amino acids. In these examples, major determinants for identities respective reside in stem; anticodon other parts tRNA dispensable aminoacylation. contrast, is a determinant identity methionine tRNA. hybrid duplexes that reconstruct acceptor-T psi C stem stem, respectively, were investigated here aminoacylation methionine. Direct visualization...
Leucyl-tRNA synthetase (LeuRS) has evolved an editing function to clear misactivated amino acids. An Escherichia coli-based assay was established identify acids that compromise the fidelity of LeuRS and translation. Multiple nonstandard as well standard were toxic cell when inactivated.
Investigations in chemical biology have focused on the synthesis of custom-designed proteins with site-specific incorporation novel amino acids. Their success requires stable production misacylated tRNAs. Utilization aminoacyl-tRNA synthetases has been hindered because enzyme molecular recognition mechanisms that ensure high fidelity protein synthesis. Leucyl-tRNA synthetase naturally misaminoacylates chemically diverse standard and nonstandard acids, but contains a separate acid editing...
ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXTRNA tetraloops as minimalist substrates for aminoacylationJian Ping Shi, Susan A. Martinis, and Paul SchimmelCite this: Biochemistry 1992, 31, 21, 4931–4936Publication Date (Print):June 1, 1992Publication History Published online1 May 2002Published inissue 1 June 1992https://pubs.acs.org/doi/10.1021/bi00136a002https://doi.org/10.1021/bi00136a002research-articleACS PublicationsRequest reuse permissionsArticle Views101Altmetric-Citations36LEARN ABOUT...
Leucyl-tRNA synthetase (LeuRS) performs dual essential roles in group I intron RNA splicing as well protein synthesis within the yeast mitochondria. Deletions of C terminus differentially impact two functions enzyme and aminoacylation vivo. Herein, we determined that a fiveamino acid C-terminal deletion LeuRS, which does not complement null strain, can form ternary complex with bI4 its maturase partner. However, fails to stimulate activity. The x-ray co-crystal structure LeuRS showed...
Aside from its catalytic function in protein synthesis, leucyl-tRNA synthetase (LRS) has a nontranslational regulating cell growth via the mammalian target of rapamycin (mTOR) complex 1 (mTORC1) pathway by sensing amino acid availability. mTOR also regulates skeletal myogenesis, but signaling mechanism is distinct that regulation. A role LRS myogenesis not been reported. Here we report negatively regulated myoblast differentiation vitro. This was independent regulation and it required...