Lawrence M Schopfer

Summary

Affiliation: University of Nebraska Medical Center
Country: USA

Publications

  1. ncbi Analytical approaches for monitoring exposure to organophosphorus and carbamate agents through analysis of protein adducts
    Lawrence M Schopfer
    Eppley Institute, University of Nebraska Medical Center, Omaha, NE 68198, USA
    Drug Test Anal 4:246-61. 2012
  2. ncbi Mass spectral characterization of organophosphate-labeled, tyrosine-containing peptides: characteristic mass fragments and a new binding motif for organophosphates
    Lawrence 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
  3. ncbi 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
  4. ncbi Reaction kinetics of biotinylated organophosphorus toxicant, FP-biotin, with human acetylcholinesterase and human butyrylcholinesterase
    Lawrence M Schopfer
    Eppley Institute, University of Nebraska Medical Center, Omaha, Nebraska 68198 6805, USA
    Chem Res Toxicol 18:747-54. 2005
  5. ncbi Development of diagnostics in the search for an explanation of aerotoxic syndrome
    Lawrence M Schopfer
    Eppley Institute, University of Nebraska Medical Center, Omaha, 68198, USA
    Anal Biochem 404:64-74. 2010
  6. ncbi Five tyrosines and two serines in human albumin are labeled by the organophosphorus agent FP-biotin
    Shi Jian Ding
    Department of Pathology and Microbiology, University of Nebraska Medical Center, Omaha, Nebraska 68198, USA
    Chem Res Toxicol 21:1787-94. 2008
  7. ncbi 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 agents
    Hasmik Grigoryan
    Eppley Institute, University of Nebraska Medical Center, 986805 Nebraska Medical Center, Omaha, NE 68198 6805, USA
    Chem Biol Interact 175:180-6. 2008
  8. ncbi Mass spectrometry identifies multiple organophosphorylated sites on tubulin
    Hasmik 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
  9. ncbi Dichlorvos, chlorpyrifos oxon and Aldicarb adducts of butyrylcholinesterase, detected by mass spectrometry in human plasma following deliberate overdose
    Bin Li
    Eppley Institute, University of Nebraska Medical Center, Omaha, NE 68198 5950, USA
    J Appl Toxicol 30:559-65. 2010
  10. ncbi Detection of adduct on tyrosine 411 of albumin in humans poisoned by dichlorvos
    Bin Li
    Eppley Institute, University of Nebraska Medical Center, Omaha, Nebraska 68198 5950, USA
    Toxicol Sci 116:23-31. 2010

Collaborators

Detail Information

Publications44

  1. ncbi Analytical approaches for monitoring exposure to organophosphorus and carbamate agents through analysis of protein adducts
    Lawrence M Schopfer
    Eppley Institute, University of Nebraska Medical Center, Omaha, NE 68198, USA
    Drug Test Anal 4:246-61. 2012
    ....
  2. ncbi Mass spectral characterization of organophosphate-labeled, tyrosine-containing peptides: characteristic mass fragments and a new binding motif for organophosphates
    Lawrence 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...
  3. ncbi 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...
  4. ncbi Reaction kinetics of biotinylated organophosphorus toxicant, FP-biotin, with human acetylcholinesterase and human butyrylcholinesterase
    Lawrence 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...
  5. ncbi Development of diagnostics in the search for an explanation of aerotoxic syndrome
    Lawrence 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...
  6. ncbi Five tyrosines and two serines in human albumin are labeled by the organophosphorus agent FP-biotin
    Shi 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...
  7. ncbi 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 agents
    Hasmik 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...
  8. ncbi Mass spectrometry identifies multiple organophosphorylated sites on tubulin
    Hasmik 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...
  9. ncbi Dichlorvos, chlorpyrifos oxon and Aldicarb adducts of butyrylcholinesterase, detected by mass spectrometry in human plasma following deliberate overdose
    Bin 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...
  10. ncbi Detection of adduct on tyrosine 411 of albumin in humans poisoned by dichlorvos
    Bin 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...
  11. ncbi Tyrosines of human and mouse transferrin covalently labeled by organophosphorus agents: a new motif for binding to proteins that have no active site serine
    Bin 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...
  12. ncbi Covalent binding of the organophosphorus agent FP-biotin to tyrosine in eight proteins that have no active site serine
    Hasmik 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...
  13. ncbi Mass spectral characterization of organophosphate-labeled lysine in peptides
    Hasmik 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...
  14. ncbi 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 carbofu
    Ellen G Duysen
    Eppley Institute, University of Nebraska Medical Center, Omaha, NE 68198 5950, USA
    Chem Biol Interact 195:189-98. 2012
    ....
  15. ncbi Pseudo-esterase activity of human albumin: slow turnover on tyrosine 411 and stable acetylation of 82 residues including 59 lysines
    Oksana 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...
  16. ncbi Binding and hydrolysis of soman by human serum albumin
    Bin 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...
  17. ncbi Carbofuran poisoning detected by mass spectrometry of butyrylcholinesterase adduct in human serum
    He 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...
  18. ncbi Matrix-assisted laser desorption/ionization time-of-flight mass spectrometry assay for organophosphorus toxicants bound to human albumin at Tyr411
    Bin 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...
  19. ncbi 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 agents
    Wei 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...
  20. ncbi Albumin, a new biomarker of organophosphorus toxicant exposure, identified by mass spectrometry
    Eric 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...
  21. ncbi Cresyl saligenin phosphate, an organophosphorus toxicant, makes covalent adducts with histidine, lysine, and tyrosine residues of human serum albumin
    Mariya 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...
  22. ncbi Aging pathways for organophosphate-inhibited human butyrylcholinesterase, including novel pathways for isomalathion, resolved by mass spectrometry
    He 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...
  23. ncbi Exposure to tri-o-cresyl phosphate detected in jet airplane passengers
    Mariya 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...
  24. ncbi Production of ES1 plasma carboxylesterase knockout mice for toxicity studies
    Ellen 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...
  25. ncbi Lamellipodin proline rich peptides associated with native plasma butyrylcholinesterase tetramers
    He 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...
  26. ncbi Reaction of human albumin with aspirin in vitro: mass spectrometric identification of acetylated lysines 199, 402, 519, and 545
    Mariya 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...
  27. ncbi Review of tyrosine and lysine as new motifs for organophosphate binding to proteins that have no active site serine
    Oksana 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...
  28. ncbi Expression of three naturally occurring genetic variants (G75R, E90D, I99M) of the BCHE gene of human butyrylcholinesterase
    Liya 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...
  29. ncbi Fast affinity purification coupled with mass spectrometry for identifying organophosphate labeled plasma butyrylcholinesterase
    He 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...
  30. ncbi Screening assays for cholinesterases resistant to inhibition by organophosphorus toxicants
    Yuxia 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...
  31. ncbi Hysteresis of butyrylcholinesterase in the approach to steady-state kinetics
    Patrick 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...
  32. ncbi Kinetic analysis of effector modulation of butyrylcholinesterase-catalysed hydrolysis of acetanilides and homologous esters
    Patrick 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...
  33. ncbi Hydrolysis of oxo- and thio-esters by human butyrylcholinesterase
    Patrick 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...
  34. ncbi A collaborative endeavor to design cholinesterase-based catalytic scavengers against toxic organophosphorus esters
    Patrick 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...
  35. ncbi DNA sequence of butyrylcholinesterase from the rat: expression of the protein and characterization of the properties of rat butyrylcholinesterase
    Andreea 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...
  36. ncbi Inhibition by allyl sulfides and phenethyl isothiocyanate of methyl-n-pentylnitrosamine depentylation by rat esophageal microsomes, human and rat CYP2E1, and Rat CYP2A3
    Chantey 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...
  37. ncbi Substrate activation in acetylcholinesterase induced by low pH or mutation in the pi-cation subsite
    Patrick 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...
  38. ncbi Butyrylcholinesterase-catalyzed hydrolysis of N-methylindoxyl acetate: analysis of volume changes upon reaction and hysteretic behavior
    Patrick 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...
  39. ncbi Aryl acylamidase activity of human serum albumin with o-nitrotrifluoroacetanilide as the substrate
    Patrick 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...
  40. ncbi Kinetic analysis of butyrylcholinesterase-catalyzed hydrolysis of acetanilides
    Patrick 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...
  41. ncbi Damped oscillatory hysteretic behaviour of butyrylcholinesterase with benzoylcholine as substrate
    Patrick 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...
  42. ncbi Rate-determining step of butyrylcholinesterase-catalyzed hydrolysis of benzoylcholine and benzoylthiocholine. Volumetric study of wild-type and D70G mutant behavior
    Patrick 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
    ....
  43. ncbi Five new naturally occurring mutations of the BCHE gene and frequencies of 12 butyrylcholinesterase alleles in a Brazilian population
    Liya 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...
  44. ncbi Mutant of Bungarus fasciatus acetylcholinesterase with low affinity and low hydrolase activity toward organophosphorus esters
    Thomas 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...