Z Radic

Summary

Affiliation: University of California
Country: USA

Publications

  1. pmc Mechanism of interaction of novel uncharged, centrally active reactivators with OP-hAChE conjugates
    Zoran Radic
    Skaggs School of Pharmacy and Pharmaceutical Sciences, University of California at San Diego, La Jolla, CA 92093 0650, USA Electronic address
    Chem Biol Interact 203:67-71. 2013
  2. doi request reprint Catalytic detoxification of nerve agent and pesticide organophosphates by butyrylcholinesterase assisted with non-pyridinium oximes
    Zoran Radic
    Skaggs School of Pharmacy and Pharmaceutical Sciences, University of California at San Diego, La Jolla, CA 92093, USA
    Biochem J 450:231-42. 2013
  3. pmc Interaction kinetics of oximes with native, phosphylated and aged human acetylcholinesterase
    Zoran Radic
    Skaggs School of Pharmacy and Pharmaceutical Sciences, University of California at San Diego, La Jolla, CA 92093 0650, United States
    Chem Biol Interact 187:163-6. 2010
  4. pmc Probing gorge dimensions of cholinesterases by freeze-frame click chemistry
    Zoran Radic
    Department of Pharmacology, Skaggs School of Pharmacy and Pharmaceutical Sciences, University of California at San Diego, 9500 Gilman Drive, La Jolla, CA 92093 0650, USA
    Chem Biol Interact 175:161-5. 2008
  5. ncbi request reprint Peripheral site ligands accelerate inhibition of acetylcholinesterase by neutral organophosphates
    Z Radic
    Department of Pharmacology, University of California at San Diego, La Jolla, CA 92093 0636, USA
    J Appl Toxicol 21:S13-4. 2001
  6. ncbi request reprint Molecular basis of interactions of cholinesterases with tight binding inhibitors
    Zoran Radic
    Department of Pharmacology 0636, University of California at San Diego, La Jolla, CA 92093, USA
    Chem Biol Interact 157:133-41. 2005
  7. ncbi request reprint The influence of peripheral site ligands on the reaction of symmetric and chiral organophosphates with wildtype and mutant acetylcholinesterases
    Z Radic
    Department of Pharmacology, University of California at San Diego, La Jolla 92093 0636, USA
    Chem Biol Interact 119:111-7. 1999
  8. ncbi request reprint Mechanism of oxime reactivation of acetylcholinesterase analyzed by chirality and mutagenesis
    L Wong
    Department of Pharmacology, University of California, San Diego, La Jolla, California 92093 0636, USA
    Biochemistry 39:5750-7. 2000
  9. pmc Theoretical analysis of the structure of the peptide fasciculin and its docking to acetylcholinesterase
    H K van den Born
    Department of Pharmacology, University of California at San Diego, La Jolla 92093 0636, USA
    Protein Sci 4:703-15. 1995
  10. ncbi request reprint Mutation of acetylcholinesterase to enhance oxime-assisted catalytic turnover of methylphosphonates
    Zrinka Kovarik
    Department of Pharmacology, University of California at San Diego, La Jolla, CA 92093 0636, USA
    Toxicology 233:79-84. 2007

Collaborators

Detail Information

Publications34

  1. pmc Mechanism of interaction of novel uncharged, centrally active reactivators with OP-hAChE conjugates
    Zoran Radic
    Skaggs School of Pharmacy and Pharmaceutical Sciences, University of California at San Diego, La Jolla, CA 92093 0650, USA Electronic address
    Chem Biol Interact 203:67-71. 2013
    ....
  2. doi request reprint Catalytic detoxification of nerve agent and pesticide organophosphates by butyrylcholinesterase assisted with non-pyridinium oximes
    Zoran Radic
    Skaggs School of Pharmacy and Pharmaceutical Sciences, University of California at San Diego, La Jolla, CA 92093, USA
    Biochem J 450:231-42. 2013
    ..The results of the present study establish that oxime-assisted catalysis is feasible for OP bioscavenging...
  3. pmc Interaction kinetics of oximes with native, phosphylated and aged human acetylcholinesterase
    Zoran Radic
    Skaggs School of Pharmacy and Pharmaceutical Sciences, University of California at San Diego, La Jolla, CA 92093 0650, United States
    Chem Biol Interact 187:163-6. 2010
    ..Dealkylation of phosphonylated enzyme, however opens space in the gorge allowing oximes to bind tighter...
  4. pmc Probing gorge dimensions of cholinesterases by freeze-frame click chemistry
    Zoran Radic
    Department of Pharmacology, Skaggs School of Pharmacy and Pharmaceutical Sciences, University of California at San Diego, 9500 Gilman Drive, La Jolla, CA 92093 0650, USA
    Chem Biol Interact 175:161-5. 2008
    ..Thus, in addition to synthesizing high affinity, lead inhibitors in situ, freeze-frame, click chemistry has capacity to generate species-specific AChE ligands that conform to the determinants in the gorge...
  5. ncbi request reprint Peripheral site ligands accelerate inhibition of acetylcholinesterase by neutral organophosphates
    Z Radic
    Department of Pharmacology, University of California at San Diego, La Jolla, CA 92093 0636, USA
    J Appl Toxicol 21:S13-4. 2001
    ....
  6. ncbi request reprint Molecular basis of interactions of cholinesterases with tight binding inhibitors
    Zoran Radic
    Department of Pharmacology 0636, University of California at San Diego, La Jolla, CA 92093, USA
    Chem Biol Interact 157:133-41. 2005
    ..These tight binding inhibitor interactions reveal useful information not only on the conformational flexibility of ChEs, but also on the diversity of modes of interaction that achieve inhibition...
  7. ncbi request reprint The influence of peripheral site ligands on the reaction of symmetric and chiral organophosphates with wildtype and mutant acetylcholinesterases
    Z Radic
    Department of Pharmacology, University of California at San Diego, La Jolla 92093 0636, USA
    Chem Biol Interact 119:111-7. 1999
    ..Analysis of inhibition by DDVP and haloxon revealed that peripheral site inhibitors increased the second order reaction rates by increasing maximal rates of phosphylation...
  8. ncbi request reprint Mechanism of oxime reactivation of acetylcholinesterase analyzed by chirality and mutagenesis
    L Wong
    Department of Pharmacology, University of California, San Diego, La Jolla, California 92093 0636, USA
    Biochemistry 39:5750-7. 2000
    ..Hence, their efficacies as reactivating agents depend on the steric bulk of the intervening groups surrounding the tetrahedral phosphorus...
  9. pmc Theoretical analysis of the structure of the peptide fasciculin and its docking to acetylcholinesterase
    H K van den Born
    Department of Pharmacology, University of California at San Diego, La Jolla 92093 0636, USA
    Protein Sci 4:703-15. 1995
    ..This approach has led to testable models for the orientation and site of bound fasciculin...
  10. ncbi request reprint Mutation of acetylcholinesterase to enhance oxime-assisted catalytic turnover of methylphosphonates
    Zrinka Kovarik
    Department of Pharmacology, University of California at San Diego, La Jolla, CA 92093 0636, USA
    Toxicology 233:79-84. 2007
    ..Our results confirm that a mixture of a mutant enzyme and an oxime might serve as an in vivo catalytic scavenger of organophosphates...
  11. ncbi request reprint Nanosecond dynamics of acetylcholinesterase near the active center gorge
    Aileen E Boyd
    Department of Pharmacology, University of California, La Jolla, California 92093 0636, USA
    J Biol Chem 279:26612-8. 2004
    ....
  12. ncbi request reprint Mutant cholinesterases possessing enhanced capacity for reactivation of their phosphonylated conjugates
    Zrinka Kovarik
    Department of Pharmacology, University of California at San Diego, La Jolla, California 92093 0636, USA
    Biochemistry 43:3222-9. 2004
    ..Rates of reactivation reach values sufficient for consideration of mixtures of a mutant enzyme and an oxime as a scavenging strategy in protection and treatment of organophosphate exposure...
  13. pmc Acetylcholinesterase active centre and gorge conformations analysed by combinatorial mutations and enantiomeric phosphonates
    Zrinka Kovarik
    Department of Pharmacology, University of California at San Diego, La Jolla, CA 92093 0636, USA
    Biochem J 373:33-40. 2003
    ..Rather, the individual aromatic residues may mutually interact to confer a distinctive stereospecificity pattern towards organophosphates...
  14. ncbi request reprint Interaction kinetics of reversible inhibitors and substrates with acetylcholinesterase and its fasciculin 2 complex
    Z Radic
    Department of Pharmacology, University of California San Diego, La Jolla, CA 92093 0636, USA
    J Biol Chem 276:4622-33. 2001
    ..Conformational flexibility appears critical for facilitating ligand passage in the narrow active center gorge for both AChE and the AChE.Fas2 complex...
  15. ncbi request reprint Reversibly bound and covalently attached ligands induce conformational changes in the omega loop, Cys69-Cys96, of mouse acetylcholinesterase
    J Shi
    Department of Pharmacology, University of California, San Diego, La Jolla, California 92093, USA
    J Biol Chem 276:42196-204. 2001
    ..Thus, combined kinetic and spectroscopic analyses provide strong evidence that conformational changes of the Omega loop accompany ligand binding...
  16. ncbi request reprint Rapid binding of a cationic active site inhibitor to wild type and mutant mouse acetylcholinesterase: Brownian dynamics simulation including diffusion in the active site gorge
    S Tara
    Department of Chemistry and Biochemistry, University of California, San Diego, La Jolla 92093 0365, USA
    Biopolymers 46:465-74. 1998
    ..Asp74 traps the ligand within the gorge, and in this way helps to ensure a reaction...
  17. pmc Investigating the structural influence of surface mutations on acetylcholinesterase inhibition by organophosphorus compounds and oxime reactivation
    Tuba Küçükkilinç
    Skaggs School of Pharmacy and Pharmaceutical Sciences, University of California at San Diego, La Jolla, CA 92093 0650, USA
    Chem Biol Interact 187:238-40. 2010
    ..These results indicate that selected residues outside the active center influence inhibition, reactivation and catalysis rates through longer range interactions...
  18. pmc Tetrameric mouse acetylcholinesterase: continuum diffusion rate calculations by solving the steady-state Smoluchowski equation using finite element methods
    Deqiang Zhang
    Howard Hughes Medical Institute, University of California at San Diego, La Jolla, California 92093, USA
    Biophys J 88:1659-65. 2005
    ..This study also shows that the finite element solver is well suited for solving the diffusion problem within complicated geometries...
  19. pmc Conformational transitions in protein-protein association: binding of fasciculin-2 to acetylcholinesterase
    Jennifer M Bui
    Department of Chemistry and Biochemistry, Howard Hughes Medical Institute, University of California, San Diego, La Jolla, California 92093 0365, USA
    Biophys J 90:3280-7. 2006
    ..It seems likely that the more stable apo form binds rapidly to AChE and conformational readjustments then occur in the resulting encounter complex...
  20. pmc Continuum simulations of acetylcholine diffusion with reaction-determined boundaries in neuromuscular junction models
    Yuhui Cheng
    Department of Chemistry and Biochemistry, Center for Theoretical Biological Physics, National Biomedical Computation Resource, University of California San Diego, 9500 Gilman Drive, La Jolla, CA 92093 0365, USA
    Biophys Chem 127:129-39. 2007
    ..The finite element method has demonstrated its flexibility and robustness in modeling large biological systems...
  21. ncbi request reprint Application of recombinant DNA methods for production of cholinesterases as organophosphate antidotes and detectors
    Palmer Taylor
    Skaggs School of Pharmacy and Pharmaceutical Sciences, University of California, San Diego, La Jolla, CA 92093 0657, USA
    Arh Hig Rada Toksikol 58:339-45. 2007
    ....
  22. ncbi request reprint Acetylcholinesterase: mechanisms of covalent inhibition of wild-type and H447I mutant determined by computational analyses
    Yuhui Cheng
    Howard Hughes Medical Institute, Department of Chemistry and Biochemistry, University of California at San Diego, La Jolla, CA 92093 0365, USA
    J Am Chem Soc 129:6562-70. 2007
    ..Taken together, our computational studies confirm that TFK0 is almost inactive in the H447I mutant and also provide detailed mechanistic insights into the experimental observations...
  23. pmc Acetylcholinesterase: converting a vulnerable target to a template for antidotes and detection of inhibitor exposure
    Palmer Taylor
    Department of Pharmacology, Skaggs School of Pharmacy and Pharmaceutical Sciences, University of California, San Diego, La Jolla, CA 92093 0650, USA
    Toxicology 233:70-8. 2007
    ..Since external reagents do not have to be added to detect the fluorescence change, the modified enzyme would serve as a remote sensor...
  24. pmc Contemporary paradigms for cholinergic ligand design guided by biological structure
    Palmer Taylor
    Department of Pharmacology, University of California San Diego, 9500 Gilman Drive, La Jolla, CA 92093 0636, USA
    Bioorg Med Chem Lett 14:1875-7. 2004
    ..Conformation and fluctuations in receptor structure are critical to ligand selectivity, and we present here how a flexible receptor template can be used in the development of selective ligands affecting cholinergic neurotransmission...
  25. ncbi request reprint Click chemistry in situ: acetylcholinesterase as a reaction vessel for the selective assembly of a femtomolar inhibitor from an array of building blocks
    Warren G Lewis
    Department of Chemistry, The Scripps Research Institute, 10550 North Torrey Pines Road, La Jolla, CA 92037, USA
    Angew Chem Int Ed Engl 41:1053-7. 2002
  26. ncbi request reprint In situ click chemistry: enzyme inhibitors made to their own specifications
    Roman Manetsch
    Contribution from the Department of Chemistry and The Skaggs Institute for Chemical Biology, The Scripps Research Institute, 10550 North Torrey Pines Road, La Jolla, CA 92037, USA
    J Am Chem Soc 126:12809-18. 2004
    ..All in situ-generated compounds were extremely potent AChE inhibitors, because of the presence of multiple sites of interaction, which include the newly formed triazole nexus as a significant pharmacophore...
  27. pmc The cholinesterases: analysis by pharmacogenomics in man
    A M Valle
    Department of Pharmacology, Skaggs School of Pharmacy and Pharmaceutical Sciences, University of California San Diego, 9500 Gilman Drive, La Jolla, CA 92093, USA
    Chem Biol Interact 175:343-5. 2008
    ..To date 19 SNPs have been identified by the re-sequencing of AChE including four nonsynonymous coding SNPs (cSNPs)...
  28. pmc Acetylcholinesterase: mechanisms of covalent inhibition of H447I mutant determined by computational analyses
    Y H Cheng
    Howard Hughes Medical Institute, Department of Chemistry and Biochemistry, University of California at San Diego, 9500 Gilman Drive, La Jolla, CA 92093 0365, USA
    Chem Biol Interact 175:196-9. 2008
    ..Taken together our computational studies confirm that TFK(0) is almost inactive in the H447I mutant, and also provide detailed mechanistic insights into the experimental observations...
  29. ncbi request reprint Structural and ligand recognition characteristics of an acetylcholine-binding protein from Aplysia californica
    Scott B Hansen
    Department of Pharmacology, University of California, San Diego, La Jolla 92093 0636, USA
    J Biol Chem 279:24197-202. 2004
    ..Hence, the two soluble proteins from mollusks, which can be studied by a variety of physical methods, become discrete surrogate proteins for the extracellular domains of distinct subtypes of nicotinic acetylcholine receptors...
  30. ncbi request reprint In situ selection of lead compounds by click chemistry: target-guided optimization of acetylcholinesterase inhibitors
    Antoni Krasinski
    Department of Chemistry and The Skaggs Institute for Chemical Biology, The Scripps Research Institute, 10550 North Torrey Pines Road, La Jolla, CA 92037, USA
    J Am Chem Soc 127:6686-92. 2005
    ..Remarkably, despite the high binding affinity, the enzyme displayed a surprisingly low preference for one PIQ enantiomer over the other...
  31. pmc Atomic interactions of neonicotinoid agonists with AChBP: molecular recognition of the distinctive electronegative pharmacophore
    Todd T Talley
    Department of Pharmacology, Skaggs School of Pharmacy and Pharmaceutical Sciences, University of California at San Diego, La Jolla, CA 99093 0657, USA
    Proc Natl Acad Sci U S A 105:7606-11. 2008
    ..This template defines the association of interacting amino acids and their energetic contributions to the distinctive interactions of neonicotinoids...
  32. ncbi request reprint Acetylcholinesterase mutants: oxime-assisted catalytic scavengers of organophosphonates
    Zrinka Kovarik
    Department of Pharmacology, University of California at San Diego, La Jolla, CA 92093 0636, USA
    Chem Biol Interact 157:388-90. 2005
  33. ncbi request reprint A mutation linked with autism reveals a common mechanism of endoplasmic reticulum retention for the alpha,beta-hydrolase fold protein family
    Antonella De Jaco
    Department of Pharmacology, University of California San Diego, La Jolla, California 92093 0636, USA
    J Biol Chem 281:9667-76. 2006
    ..The mutation may alter the capacity of these proteins to dissociate from their chaperone prior to oligomerization and processing for export...
  34. ncbi request reprint Influence of agonists and antagonists on the segmental motion of residues near the agonist binding pocket of the acetylcholine-binding protein
    Ryan E Hibbs
    Department of Pharmacology, University of California San Diego, La Jolla, California 92093, USA
    J Biol Chem 281:39708-18. 2006
    ..The results reveal that agonists and antagonists produced distinctive changes in the flexibility of a portion of loop F...