Research Topics
| Z RadicSummaryAffiliation: University of California Country: USA Publications
| Collaborators
|
Detail Information
Publications
Mechanism of interaction of novel uncharged, centrally active reactivators with OP-hAChE conjugatesZoran 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....- Catalytic detoxification of nerve agent and pesticide organophosphates by butyrylcholinesterase assisted with non-pyridinium oximesZoran 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... 
Interaction kinetics of oximes with native, phosphylated and aged human acetylcholinesteraseZoran 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...- Probing gorge dimensions of cholinesterases by freeze-frame click chemistryZoran 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... 
Peripheral site ligands accelerate inhibition of acetylcholinesterase by neutral organophosphatesZ Radic
Department of Pharmacology, University of California at San Diego, La Jolla, CA 92093 0636, USA
J Appl Toxicol 21:S13-4. 2001....- Molecular basis of interactions of cholinesterases with tight binding inhibitorsZoran 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... - The influence of peripheral site ligands on the reaction of symmetric and chiral organophosphates with wildtype and mutant acetylcholinesterasesZ 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... - Mechanism of oxime reactivation of acetylcholinesterase analyzed by chirality and mutagenesisL 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... - Theoretical analysis of the structure of the peptide fasciculin and its docking to acetylcholinesteraseH 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... - Mutation of acetylcholinesterase to enhance oxime-assisted catalytic turnover of methylphosphonatesZrinka 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... - Nanosecond dynamics of acetylcholinesterase near the active center gorgeAileen E Boyd
Department of Pharmacology, University of California, La Jolla, California 92093 0636, USA
J Biol Chem 279:26612-8. 2004.... - Mutant cholinesterases possessing enhanced capacity for reactivation of their phosphonylated conjugatesZrinka 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... - Acetylcholinesterase active centre and gorge conformations analysed by combinatorial mutations and enantiomeric phosphonatesZrinka 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... - Interaction kinetics of reversible inhibitors and substrates with acetylcholinesterase and its fasciculin 2 complexZ 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... - Reversibly bound and covalently attached ligands induce conformational changes in the omega loop, Cys69-Cys96, of mouse acetylcholinesteraseJ 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... - Rapid binding of a cationic active site inhibitor to wild type and mutant mouse acetylcholinesterase: Brownian dynamics simulation including diffusion in the active site gorgeS 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... - Investigating the structural influence of surface mutations on acetylcholinesterase inhibition by organophosphorus compounds and oxime reactivationTuba 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... - Tetrameric mouse acetylcholinesterase: continuum diffusion rate calculations by solving the steady-state Smoluchowski equation using finite element methodsDeqiang 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... - Conformational transitions in protein-protein association: binding of fasciculin-2 to acetylcholinesteraseJennifer 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... - Continuum simulations of acetylcholine diffusion with reaction-determined boundaries in neuromuscular junction modelsYuhui 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... - Application of recombinant DNA methods for production of cholinesterases as organophosphate antidotes and detectorsPalmer 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.... - Acetylcholinesterase: mechanisms of covalent inhibition of wild-type and H447I mutant determined by computational analysesYuhui 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... - Acetylcholinesterase: converting a vulnerable target to a template for antidotes and detection of inhibitor exposurePalmer 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... - Contemporary paradigms for cholinergic ligand design guided by biological structurePalmer 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... - Click chemistry in situ: acetylcholinesterase as a reaction vessel for the selective assembly of a femtomolar inhibitor from an array of building blocksWarren 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 - In situ click chemistry: enzyme inhibitors made to their own specificationsRoman 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... - The cholinesterases: analysis by pharmacogenomics in manA 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)... - Acetylcholinesterase: mechanisms of covalent inhibition of H447I mutant determined by computational analysesY 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... - Structural and ligand recognition characteristics of an acetylcholine-binding protein from Aplysia californicaScott 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... - In situ selection of lead compounds by click chemistry: target-guided optimization of acetylcholinesterase inhibitorsAntoni 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... - Atomic interactions of neonicotinoid agonists with AChBP: molecular recognition of the distinctive electronegative pharmacophoreTodd 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... - Acetylcholinesterase mutants: oxime-assisted catalytic scavengers of organophosphonatesZrinka Kovarik
Department of Pharmacology, University of California at San Diego, La Jolla, CA 92093-0636, USA
Chem Biol Interact 157:388-90. 2005 - A mutation linked with autism reveals a common mechanism of endoplasmic reticulum retention for the alpha,beta-hydrolase fold protein familyAntonella 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... - Influence of agonists and antagonists on the segmental motion of residues near the agonist binding pocket of the acetylcholine-binding proteinRyan 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...