Research Topics
Genomes and Genes | Lawrence M SchopferSummaryAffiliation: University of Nebraska Medical Center Country: USA Publications
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Publications
Analytical approaches for monitoring exposure to organophosphorus and carbamate agents through analysis of protein adductsLawrence M Schopfer
Eppley Institute, University of Nebraska Medical Center, Omaha, NE 68198, USA
Drug Test Anal 4:246-61. 2012....
Mass spectral characterization of organophosphate-labeled, tyrosine-containing peptides: characteristic mass fragments and a new binding motif for organophosphatesLawrence M Schopfer
Eppley Institute, University of Nebraska Medical Center, Omaha, NE 68198 6805, USA
J Chromatogr B Analyt Technol Biomed Life Sci 878:1297-311. 2010..Modified peptides are difficult to find when the OP bears no radiolabel and no tag. The characteristic MSMS fragment ions are valuable because they are identifiers for OP-tyrosine, independent of the peptide...
Characteristic mass spectral fragments of the organophosphorus agent FP-biotin and FP-biotinylated peptides from trypsin and bovine albumin (Tyr410)Lawrence M Schopfer
University of Nebraska Medical Center, Eppley Institute, Omaha, NE 68198, USA
Anal Biochem 345:122-32. 2005..This latter result confirms that the organophosphorus binding site of albumin is a tyrosine. This method can be used to search for new biomarkers of organophosphorus agent exposure...
Reaction kinetics of biotinylated organophosphorus toxicant, FP-biotin, with human acetylcholinesterase and human butyrylcholinesteraseLawrence M Schopfer
Eppley Institute, University of Nebraska Medical Center, Omaha, Nebraska 68198 6805, USA
Chem Res Toxicol 18:747-54. 2005..The binding affinity was estimated to be >85 nM for AChE and >5.8 nM for BChE. It was concluded that FP-biotin is a potent OP, well-suited for searching for new biomarkers of OP exposure...
Development of diagnostics in the search for an explanation of aerotoxic syndromeLawrence M Schopfer
Eppley Institute, University of Nebraska Medical Center, Omaha, 68198, USA
Anal Biochem 404:64-74. 2010..It is concluded that toxic gases or oil mists in cabin air may form adducts on plasma butyrylcholinesterase and albumin, detectable by mass spectrometry...
Five tyrosines and two serines in human albumin are labeled by the organophosphorus agent FP-biotinShi Jian Ding
Department of Pathology and Microbiology, University of Nebraska Medical Center, Omaha, Nebraska 68198, USA
Chem Res Toxicol 21:1787-94. 2008..Diethoxyphosphate-labeled Tyr 411 was stable for months at pH 7.4. These results will be useful in the development of specific antibodies to detect OP exposure and to engineer albumin for use as an OP scavenger...
Mass spectrometry identifies covalent binding of soman, sarin, chlorpyrifos oxon, diisopropyl fluorophosphate, and FP-biotin to tyrosines on tubulin: a potential mechanism of long term toxicity by organophosphorus agentsHasmik Grigoryan
Eppley Institute, University of Nebraska Medical Center, 986805 Nebraska Medical Center, Omaha, NE 68198 6805, USA
Chem Biol Interact 175:180-6. 2008..It is concluded that OP bind covalently to tubulin, and that this binding could explain cognitive impairment associated with OP exposure...
Mass spectrometry identifies multiple organophosphorylated sites on tubulinHasmik Grigoryan
University of Nebraska Medical Center, Eppley Institute for Cancer Research, 986805 Nebraska Medical Center, Omaha, NE 68198 6805, USA
Toxicol Appl Pharmacol 240:149-58. 2009..In conclusion seventeen tyrosines in tubulin have the potential to covalently bind chlorpyrifos oxon. These results will be useful when searching for OP-labeled tubulin in live animals...
Dichlorvos, chlorpyrifos oxon and Aldicarb adducts of butyrylcholinesterase, detected by mass spectrometry in human plasma following deliberate overdoseBin Li
Eppley Institute, University of Nebraska Medical Center, Omaha, NE 68198 5950, USA
J Appl Toxicol 30:559-65. 2010..In conclusion, a mass spectrometry method for identification of exposure to live toxic pesticides has been developed, based on identification of pesticide adducts on the active site serine of human butyrylcholinesterase...
Detection of adduct on tyrosine 411 of albumin in humans poisoned by dichlorvosBin Li
Eppley Institute, University of Nebraska Medical Center, Omaha, Nebraska 68198 5950, USA
Toxicol Sci 116:23-31. 2010..Identification of other OP-modified proteins may lead to an understanding of neurotoxic symptoms that appear long after the initial OP exposure...
Tyrosines of human and mouse transferrin covalently labeled by organophosphorus agents: a new motif for binding to proteins that have no active site serineBin Li
Eppley Institute, University of Nebraska Medical Center, Omaha, Nebraska 68198 6805, USA
Toxicol Sci 107:144-55. 2009..The extent to which tyrosine modification by OP can occur in vivo and the toxicological implications of such modifications require further investigation...
Covalent binding of the organophosphorus agent FP-biotin to tyrosine in eight proteins that have no active site serineHasmik Grigoryan
Eppley Institute, University of Nebraska Medical Center, 986805 Nebraska Medical Center, Omaha, NE 68198 6805, United States
Chem Biol Interact 180:492-8. 2009..Another application is in the search for biomarkers of organophosphorus agent exposure. Previous searches have been limited to serine hydrolases. Now proteins such as albumin and keratin can be considered...
Mass spectral characterization of organophosphate-labeled lysine in peptidesHasmik Grigoryan
Eppley Institute, University of Nebraska Medical Center, Omaha, NE 68198, USA
Anal Biochem 394:92-100. 2009..0, 181.2, and 83.8amu. This new OP-binding motif to lysine suggests new directions to search for mechanisms of long-term effects of OP exposure and in the search for biomarkers of OP exposure...
Differential sensitivity of plasma carboxylesterase-null mice to parathion, chlorpyrifos and chlorpyrifos oxon, but not to diazinon, dichlorvos, diisopropylfluorophosphate, cresyl saligenin phosphate, cyclosarin thiocholine, tabun thiocholine, and carbofuEllen G Duysen
Eppley Institute, University of Nebraska Medical Center, Omaha, NE 68198 5950, USA
Chem Biol Interact 195:189-98. 2012....
Pseudo-esterase activity of human albumin: slow turnover on tyrosine 411 and stable acetylation of 82 residues including 59 lysinesOksana Lockridge
Eppley Institute, University of Nebraska Medical Center, Omaha, Nebraska 68198, USA
J Biol Chem 283:22582-90. 2008..Acetylated lysines formed adducts that were even more stable. In conclusion, the pseudo-esterase activity of albumin is the result of irreversible acetylation of 82 residues and is not the result of turnover...
Binding and hydrolysis of soman by human serum albuminBin Li
University of Nebraska Medical Center, Eppley Institute, Omaha, NE 68198 6805, USA
Chem Res Toxicol 21:421-31. 2008..Soman-albumin adducts detected by mass spectrometry could be useful for the diagnosis of soman exposure...
Carbofuran poisoning detected by mass spectrometry of butyrylcholinesterase adduct in human serumHe Li
Eppley Institute, University of Nebraska Medical Center, Omaha, NE 68198, USA
J Appl Toxicol 29:149-55. 2009..The method uses 1 ml of serum and detects low-level exposure associated with as little as 20% inhibition of plasma butyrylcholinesterase...
Matrix-assisted laser desorption/ionization time-of-flight mass spectrometry assay for organophosphorus toxicants bound to human albumin at Tyr411Bin Li
Eppley Institute, University of Nebraska Medical Center, Omaha, NE 68198, USA
Anal Biochem 361:263-72. 2007..Our results show that OP pesticides and nerve agents bind covalently to human albumin at Tyr411. The presence of Tyr411 on an exposed surface of albumin suggests that an antibody response could be generated against OP-albumin adducts...
Mice treated with chlorpyrifos or chlorpyrifos oxon have organophosphorylated tubulin in the brain and disrupted microtubule structures, suggesting a role for tubulin in neurotoxicity associated with exposure to organophosphorus agentsWei Jiang
Eppley Institute, University of Nebraska Medical Center, Omaha, Nebraska 68198 5950, USA
Toxicol Sci 115:183-93. 2010..Covalent binding of CPO to tubulin and to tubulin-associated proteins is a potential mechanism of neurotoxicity...
Albumin, a new biomarker of organophosphorus toxicant exposure, identified by mass spectrometryEric S Peeples
University of Nebraska Medical Center, Eppley Institute, Omaha, Nebraska 68198-6805, USA
Toxicol Sci 83:303-12. 2005..Carboxylesterase is not a biomarker in man because humans have no carboxylesterase in blood. It is concluded that OP bound to albumin could serve as a new biomarker of OP exposure in man...
Cresyl saligenin phosphate, an organophosphorus toxicant, makes covalent adducts with histidine, lysine, and tyrosine residues of human serum albuminMariya S Liyasova
Department of Environmental, Agricultural and Occupational Health, University of Nebraska Medical Center, Omaha, NE 68198 5950, USA
Chem Res Toxicol 25:1752-61. 2012..The o-hydroxybenzyl adduct on histidine is novel. The ability of CBDP to form stable adducts on histidine, tyrosine, and lysine allows one to consider new mechanisms of toxicity from TOCP exposure...
Aging pathways for organophosphate-inhibited human butyrylcholinesterase, including novel pathways for isomalathion, resolved by mass spectrometryHe Li
Eppley Institute and Department of Biochemistry and Molecular Biology, University of Nebraska Medical Center, Omaha, Nebraska 68198 6805, USA
Toxicol Sci 100:136-45. 2007..e., the classical X-R scission pathway. In contrast, isomalathion aged through both X-R and P-X pathways; the main aged product resulted from P-S bond cleavage and a minor product resulted from O-C and/or S-C bond cleavage...
Exposure to tri-o-cresyl phosphate detected in jet airplane passengersMariya Liyasova
Eppley Institute, University of Nebraska Medical Center, Omaha, NE 68198 5950, USA
Toxicol Appl Pharmacol 256:337-47. 2011..In conclusion, this is the first report of an assay that detects exposure to tri-o-cresyl phosphate in jet airplane travelers...
Production of ES1 plasma carboxylesterase knockout mice for toxicity studiesEllen G Duysen
Eppley Institute, University of Nebraska Medical Center, Omaha, Nebraska 68198 5950, USA
Chem Res Toxicol 24:1891-8. 2011..The ES1-/- mouse should be an appropriate model for testing highly toxic nerve agents and for evaluating protection strategies against the toxicity of nerve agents...
Lamellipodin proline rich peptides associated with native plasma butyrylcholinesterase tetramersHe Li
Eppley Institute and Department of Biochemistry and Molecular Biology, University of Nebraska Medical Center, Omaha, NE 68198 6805, USA
Biochem J 411:425-32. 2008..We propose that the proline-rich peptides organize the 4 subunits of BChE into a 340 kDa tetramer, by interacting with the C-terminal BChE tetramerization domain...
Reaction of human albumin with aspirin in vitro: mass spectrometric identification of acetylated lysines 199, 402, 519, and 545Mariya S Liyasova
University of Nebraska Medical Center, Department of Environmental, Agricultural and Occupational Health, Omaha, NE 68198 6805, USA
Biochem Pharmacol 79:784-91. 2010..It was concluded that the aspirin esterase activity of albumin is a pseudo-esterase activity in which aspirin stably acetylates lysines and releases salicylate...
Review of tyrosine and lysine as new motifs for organophosphate binding to proteins that have no active site serineOksana Lockridge
Eppley Institute, 985950 University of Nebraska Medical Center, Omaha, NE 68198 5950, United States
Chem Biol Interact 187:344-8. 2010..Treatment of neurodegenerative disorders could be developed by identifying methods to reverse OP binding to tyrosine...
Expression of three naturally occurring genetic variants (G75R, E90D, I99M) of the BCHE gene of human butyrylcholinesteraseLiya R Mikami
aDepartment of Genetics, Federal University of Parana, Curitiba, Parana, Brasil bEppley Institute, University of Nebraska Medical Center, Omaha, Nebraska, USA
Pharmacogenet Genomics 17:681-5. 2007..BChE genotyping may become important for estimating prognosis, and the knowledge of the genetic variants of BChE in a particular population may be useful for carrying out the genotyping assays...
Fast affinity purification coupled with mass spectrometry for identifying organophosphate labeled plasma butyrylcholinesteraseHe Li
Eppley Institute, University of Nebraska Medical Center, Omaha, NE 68198 6805, USA
Chem Biol Interact 175:68-72. 2008..The 29 residue active site tryptic peptide labeled with the nerve agents soman or sarin was identified...
Screening assays for cholinesterases resistant to inhibition by organophosphorus toxicantsYuxia Wang
University of Nebraska Medical Center, Eppley Institute, Omaha, NE 68198-6805, USA
Anal Biochem 329:131-8. 2004..Both wild-type and G117H BChE were in the epithelial cells of the villi. These assays can be used to identify OP-resistant cholinesterases in culture medium and in animal tissues...
Hysteresis of butyrylcholinesterase in the approach to steady-state kineticsPatrick Masson
Centre de Recherches du Service de Sante des Armees, BP 87, 38702 La Tronche Cedex, France
Chem Biol Interact 157:143-52. 2005..Therefore, a physiological or toxicological relevance for the hysteresis in BChE cannot be ruled out...
Kinetic analysis of effector modulation of butyrylcholinesterase-catalysed hydrolysis of acetanilides and homologous estersPatrick Masson
Unite d Enzymologie, Departement de Toxicologie, Centre de Recherches du Service de Sante des Armees, La Tronche Cedex, France
FEBS J 275:2617-31. 2008..The complex inhibition/activation effects of effectors, depending on the integrity of the peripheral anionic site, reflect the allosteric 'cross-talk' between the peripheral anionic site and the catalytic centre...
Hydrolysis of oxo- and thio-esters by human butyrylcholinesterasePatrick Masson
Centre de Recherches du Service de Sante des Armees, Unite d Enzymologie, BP 87, 38702 La Tronche Cedex, France
Biochim Biophys Acta 1774:16-34. 2007..Interaction of these groups with the ethereal hetero-atom can have a neutral, an additive or an antagonistic effect on transition state stabilization, depending on their molecular structure, size and enantiomeric configuration...
A collaborative endeavor to design cholinesterase-based catalytic scavengers against toxic organophosphorus estersPatrick Masson
Toxicology Department, Enzymology Unit, Centre de Recherches du Service de Sante des Armees, La Tronche Cedex, France
Chem Biol Interact 175:273-80. 2008..Additional mutations were made for optimizing activity of the new dyad. It is anticipated that these new mutants will have OP hydrolase activity...
DNA sequence of butyrylcholinesterase from the rat: expression of the protein and characterization of the properties of rat butyrylcholinesteraseAndreea Ticu Boeck
Eppley Institute, 986805, University of Nebraska Medical Center, Omaha, NE 68198 6805, USA
Biochem Pharmacol 63:2101-10. 2002..3hr. Human serum contains 5mg/L of BChE and 0.01mg/L of AChE. Male rat serum contains 0.2mg/L of BChE and approximately 0.2mg/L of AChE...
Inhibition by allyl sulfides and phenethyl isothiocyanate of methyl-n-pentylnitrosamine depentylation by rat esophageal microsomes, human and rat CYP2E1, and Rat CYP2A3Chantey R Morris
Eppley Institute for Research in Cancer, Omaha, Nebraska 68198, USA
Nutr Cancer 48:54-63. 2004..7-70 microM for inhibition by DADS. With PEITC, Ki for MPN depentylation by REM, rat CYP2E1, and rat CYP2A3 was 0.4-4.6 microM. These low Ki and IC50 values may help explain how garlic and Cruciferae inhibit carcinogenesis...
Substrate activation in acetylcholinesterase induced by low pH or mutation in the pi-cation subsitePatrick Masson
Centre de Recherches du Service de Sante des Armees, Unite d Enzymologie, La Tronche Cedex, France
Biochim Biophys Acta 1594:313-24. 2002..The finding that AChE is activated by excess substrate supports the idea that binding of a second substrate molecule to the PAS induces a conformational change that reorganizes the active site...
Butyrylcholinesterase-catalyzed hydrolysis of N-methylindoxyl acetate: analysis of volume changes upon reaction and hysteretic behaviorPatrick Masson
Centre de Recherches du Service de Sante des Armees, Unite d Enzymologie, BP 87, 24 Av Maquis du Gresivaudan, 38702 La Tronche Cedex, France
Biochim Biophys Acta 1597:229-43. 2002..The E-->E' transition is accompanied by a negative activation volume (DeltaV++(0)= -45+/-10 ml/mol), and the E' form is more compact than E. Hydration water in the gorge of E' appears to be more structured than in the unprimed form...
Aryl acylamidase activity of human serum albumin with o-nitrotrifluoroacetanilide as the substratePatrick Masson
Centre de Recherches du Service de Sante des Armees, Unite d Enzymologie, BP 87, 38702 La Tronche Cedex, France
J Enzyme Inhib Med Chem 22:463-9. 2007..6-1 mM), albumin may participate in hydrolysis of aryl acylamides through second-order kinetics. This suggests that albumin may have a role in the metabolism of endogenous and exogenous aromatic amides, including drugs and xenobiotics...
Kinetic analysis of butyrylcholinesterase-catalyzed hydrolysis of acetanilidesPatrick Masson
Centre de Recherches du Service de Sante des Armees, Departement de Toxicologie, Unite d Enzymologie, BP 87, 38702 La Tronche Cedex, France
Biochim Biophys Acta 1774:1139-47. 2007..It was concluded that the active sites for esterase and AAA activities are identical, i.e. S198. This excludes any other residue present in the gorge for being the catalytic nucleophile pole...
Damped oscillatory hysteretic behaviour of butyrylcholinesterase with benzoylcholine as substratePatrick Masson
Centre de Recherches du Service de Sante des Armees, Departement de Toxicologie, Unite d Enzymologie, La Tronche, France
Eur J Biochem 271:220-34. 2004..1H-NMR measurements provided evidence for a slow equilibrium between two BzCh conformers. Binding of the conformationally preferred substrate conformer leads to products...
Rate-determining step of butyrylcholinesterase-catalyzed hydrolysis of benzoylcholine and benzoylthiocholine. Volumetric study of wild-type and D70G mutant behaviorPatrick Masson
Centre de Recherches du Service de Santé des Armées CRSSA, Departement de Toxicologie, Unite d Enzymologie, 38702 La Tronche Cedex, France
Eur J Biochem 271:1980-90. 2004....
Five new naturally occurring mutations of the BCHE gene and frequencies of 12 butyrylcholinesterase alleles in a Brazilian populationLiya R Mikami
Department of Genetics, Federal University of Parana, Curitiba, Parana, Brazil
Pharmacogenet Genomics 18:213-8. 2008..Gene expression showed that only one of the newly identified mutations (G333C) altered BChE activity, leading to a decrease of about 80% in relation to the wild-type enzyme...
Mutant of Bungarus fasciatus acetylcholinesterase with low affinity and low hydrolase activity toward organophosphorus estersThomas Poyot
Departement de Toxicologie, Centre de Recherches du Service de Sante des Armees, BP 87, 38702 La Tronche Cedex, France
Biochim Biophys Acta 1764:1470-8. 2006..DFP was characterised as a slow-binding substrate. This mutant is the first mutant of AChE capable of hydrolysing organophosphates. However, the overall OPase efficiency was greatly decreased compared to G117H butyrylcholinesterase...
