{"id":"https://openalex.org/W2059934454","doi":"https://doi.org/10.1021/ja970395v","title":"On the Mechanism of Acetylcholinesterase Action: The Electrostatically Induced Acceleration of the Catalytic Acylation Step","display_name":"On the Mechanism of Acetylcholinesterase Action: The Electrostatically Induced Acceleration of the Catalytic Acylation Step","publication_year":1997,"publication_date":"1997-09-01","ids":{"openalex":"https://openalex.org/W2059934454","doi":"https://doi.org/10.1021/ja970395v","mag":"2059934454"},"language":"en","primary_location":{"id":"doi:10.1021/ja970395v","doi":"https://doi.org/10.1021/ja970395v","is_oa":false,"landing_page_url":"https://doi.org/10.1021/ja970395v","pdf_url":null,"source":{"id":"https://openalex.org/S111155417","display_name":"Journal of the American Chemical Society","issn_l":"0002-7863","issn":["0002-7863","1520-5126","1943-2984"],"is_oa":false,"is_in_doaj":false,"is_core":true,"listed_in":["cwts-core","dongbi-a","jufo-3","ki-jl-3","medline","norway-2","poland-200","russia-white-list-1","vabb-shw"],"host_organization":"https://openalex.org/P4310320006","host_organization_name":"American Chemical Society","host_organization_lineage":["https://openalex.org/P4310320006"],"host_organization_lineage_names":["American Chemical Society"],"type":"journal"},"license":null,"license_id":null,"version":"publishedVersion","is_accepted":true,"is_published":true,"raw_source_name":"Journal of the American Chemical Society","raw_type":"journal-article"},"volume":null,"type":"article","is_traditional":true,"indexed_in":["crossref"],"open_access":{"is_oa":false,"oa_status":"closed","oa_url":null,"any_repository_has_fulltext":false},"authorships":[{"author_position":"first","author":{"id":"https://openalex.org/A5111387695","display_name":"Stanislaw T. Wlodek","orcid":null,"observed_orcids":[]},"institutions":[{"id":"https://openalex.org/I36258959","display_name":"University of California San Diego","ror":"https://ror.org/0168r3w48","country_code":"US","type":"education","lineage":["https://openalex.org/I36258959"]},{"id":"https://openalex.org/I44461941","display_name":"University of Houston","ror":"https://ror.org/048sx0r50","country_code":"US","type":"education","lineage":["https://openalex.org/I44461941"]},{"id":"https://openalex.org/I4654613","display_name":"University of Warsaw","ror":"https://ror.org/039bjqg32","country_code":"PL","type":"education","lineage":["https://openalex.org/I4654613"]}],"countries":["PL","US"],"is_corresponding":false,"raw_author_name":"Stanislaw T. Wlodek","raw_affiliation_strings":["Contribution from the Texas Center for Advanced Molecular Computation, University of Houston, Houston, Texas 77204-5502, Department of Biophysics, University of Warsaw, Warsaw 02-089, Poland, and Department of Pharmacology, University of California, San Diego, La Jolla, California 92093-0365"],"raw_orcid":null,"affiliations":[{"raw_affiliation_string":"Contribution from the Texas Center for Advanced Molecular Computation, University of Houston, Houston, Texas 77204-5502, Department of Biophysics, University of Warsaw, Warsaw 02-089, Poland, and Department of Pharmacology, University of California, San Diego, La Jolla, California 92093-0365","institution_ids":["https://openalex.org/I36258959","https://openalex.org/I44461941","https://openalex.org/I4654613"]}]},{"author_position":"middle","author":{"id":"https://openalex.org/A5045570505","display_name":"Jan M. Antosiewicz","orcid":"https://orcid.org/0000-0002-9269-2192","observed_orcids":["https://orcid.org/0000-0002-9269-2192"]},"institutions":[{"id":"https://openalex.org/I36258959","display_name":"University of California San Diego","ror":"https://ror.org/0168r3w48","country_code":"US","type":"education","lineage":["https://openalex.org/I36258959"]},{"id":"https://openalex.org/I44461941","display_name":"University of Houston","ror":"https://ror.org/048sx0r50","country_code":"US","type":"education","lineage":["https://openalex.org/I44461941"]},{"id":"https://openalex.org/I4654613","display_name":"University of Warsaw","ror":"https://ror.org/039bjqg32","country_code":"PL","type":"education","lineage":["https://openalex.org/I4654613"]}],"countries":["PL","US"],"is_corresponding":false,"raw_author_name":"Jan Antosiewicz","raw_affiliation_strings":["Contribution from the Texas Center for Advanced Molecular Computation, University of Houston, Houston, Texas 77204-5502, Department of Biophysics, University of Warsaw, Warsaw 02-089, Poland, and Department of Pharmacology, University of California, San Diego, La Jolla, California 92093-0365"],"raw_orcid":null,"affiliations":[{"raw_affiliation_string":"Contribution from the Texas Center for Advanced Molecular Computation, University of Houston, Houston, Texas 77204-5502, Department of Biophysics, University of Warsaw, Warsaw 02-089, Poland, and Department of Pharmacology, University of California, San Diego, La Jolla, California 92093-0365","institution_ids":["https://openalex.org/I36258959","https://openalex.org/I44461941","https://openalex.org/I4654613"]}]},{"author_position":"last","author":{"id":"https://openalex.org/A5062602935","display_name":"James M. Briggs","orcid":"https://orcid.org/0000-0001-5863-8945","observed_orcids":["https://orcid.org/0000-0001-5863-8945"]},"institutions":[{"id":"https://openalex.org/I36258959","display_name":"University of California San Diego","ror":"https://ror.org/0168r3w48","country_code":"US","type":"education","lineage":["https://openalex.org/I36258959"]},{"id":"https://openalex.org/I44461941","display_name":"University of Houston","ror":"https://ror.org/048sx0r50","country_code":"US","type":"education","lineage":["https://openalex.org/I44461941"]},{"id":"https://openalex.org/I4654613","display_name":"University of Warsaw","ror":"https://ror.org/039bjqg32","country_code":"PL","type":"education","lineage":["https://openalex.org/I4654613"]}],"countries":["PL","US"],"is_corresponding":false,"raw_author_name":"James M. Briggs","raw_affiliation_strings":["Contribution from the Texas Center for Advanced Molecular Computation, University of Houston, Houston, Texas 77204-5502, Department of Biophysics, University of Warsaw, Warsaw 02-089, Poland, and Department of Pharmacology, University of California, San Diego, La Jolla, California 92093-0365"],"raw_orcid":null,"affiliations":[{"raw_affiliation_string":"Contribution from the Texas Center for Advanced Molecular Computation, University of Houston, Houston, Texas 77204-5502, Department of Biophysics, University of Warsaw, Warsaw 02-089, Poland, and Department of Pharmacology, University of California, San Diego, La Jolla, California 92093-0365","institution_ids":["https://openalex.org/I36258959","https://openalex.org/I44461941","https://openalex.org/I4654613"]}]}],"institutions":[],"countries_distinct_count":2,"institutions_distinct_count":3,"corresponding_author_ids":[],"corresponding_institution_ids":[],"apc_list":{"value":4500,"currency":"USD","value_usd":4500},"apc_paid":null,"fwci":1.9498,"has_fulltext":false,"cited_by_count":49,"citation_normalized_percentile":{"value":0.86210079,"is_in_top_1_percent":false,"is_in_top_10_percent":false},"cited_by_percentile_year":{"min":88,"max":98},"biblio":{"volume":"119","issue":"35","first_page":"8159","last_page":"8165"},"is_retracted":false,"is_paratext":false,"is_xpac":false,"primary_topic":{"id":"https://openalex.org/T12023","display_name":"Cholinesterase and Neurodegenerative Diseases","score":0.6425999999046326,"subfield":{"id":"https://openalex.org/subfields/2736","display_name":"Pharmacology (medical)"},"field":{"id":"https://openalex.org/fields/27","display_name":"Medicine"},"domain":{"id":"https://openalex.org/domains/4","display_name":"Health Sciences"}},"topics":[{"id":"https://openalex.org/T12023","display_name":"Cholinesterase and Neurodegenerative Diseases","score":0.6425999999046326,"subfield":{"id":"https://openalex.org/subfields/2736","display_name":"Pharmacology (medical)"},"field":{"id":"https://openalex.org/fields/27","display_name":"Medicine"},"domain":{"id":"https://openalex.org/domains/4","display_name":"Health Sciences"}},{"id":"https://openalex.org/T12191","display_name":"Physical Organic Chemistry and Reaction Kinetics","score":0.34450000524520874,"subfield":{"id":"https://openalex.org/subfields/1605","display_name":"Organic Chemistry"},"field":{"id":"https://openalex.org/fields/16","display_name":"Chemistry"},"domain":{"id":"https://openalex.org/domains/3","display_name":"Physical Sciences"}},{"id":"https://openalex.org/T12412","display_name":"Enzyme function and inhibition","score":0.003599999938160181,"subfield":{"id":"https://openalex.org/subfields/1312","display_name":"Molecular Biology"},"field":{"id":"https://openalex.org/fields/13","display_name":"Biochemistry, Genetics and Molecular Biology"},"domain":{"id":"https://openalex.org/domains/1","display_name":"Life Sciences"}}],"keywords":[{"id":"https://openalex.org/keywords/acetylcholinesterase","display_name":"acetylcholinesterase","score":0.9959999918937683},{"id":"https://openalex.org/keywords/torpedo-californica","display_name":"Torpedo californica","score":0.7630000114440918},{"id":"https://openalex.org/keywords/tetrahedral-intermediate","display_name":"tetrahedral intermediate","score":0.9419999718666077},{"id":"https://openalex.org/keywords/oxyanion-hole","display_name":"oxyanion hole","score":0.8399999737739563},{"id":"https://openalex.org/keywords/electrostatic-effects","display_name":"electrostatic effects","score":0.5289999842643738},{"id":"https://openalex.org/keywords/transition-state-stabilization","display_name":"transition state stabilization","score":0.6809999942779541},{"id":"https://openalex.org/keywords/enzyme-active-site","display_name":"enzyme active site","score":0.5920000076293945},{"id":"https://openalex.org/keywords/charged-substrates","display_name":"charged substrates","score":0.5440000295639038}],"concepts":[{"id":"https://openalex.org/C185592680","wikidata":"https://www.wikidata.org/wiki/Q2329","display_name":"Chemistry","level":0,"score":0.9336161017417908},{"id":"https://openalex.org/C192604958","wikidata":"https://www.wikidata.org/wiki/Q7706517","display_name":"Tetrahedral carbonyl addition compound","level":4,"score":0.7764109373092651},{"id":"https://openalex.org/C41183919","wikidata":"https://www.wikidata.org/wiki/Q423026","display_name":"Active site","level":3,"score":0.603279709815979},{"id":"https://openalex.org/C123419017","wikidata":"https://www.wikidata.org/wiki/Q7826734","display_name":"Torpedo","level":4,"score":0.5402007699012756},{"id":"https://openalex.org/C2778816929","wikidata":"https://www.wikidata.org/wiki/Q22676679","display_name":"Acetylcholinesterase","level":3,"score":0.5177637338638306},{"id":"https://openalex.org/C71240020","wikidata":"https://www.wikidata.org/wiki/Q186011","display_name":"Stereochemistry","level":1,"score":0.469833105802536},{"id":"https://openalex.org/C193557335","wikidata":"https://www.wikidata.org/wiki/Q61424","display_name":"Acylation","level":3,"score":0.4498358368873596},{"id":"https://openalex.org/C179506582","wikidata":"https://www.wikidata.org/wiki/Q7115108","display_name":"Oxyanion hole","level":4,"score":0.42950439453125},{"id":"https://openalex.org/C2781442258","wikidata":"https://www.wikidata.org/wiki/Q46310","display_name":"Ab initio","level":2,"score":0.423308789730072},{"id":"https://openalex.org/C56856141","wikidata":"https://www.wikidata.org/wiki/Q883112","display_name":"Enzyme kinetics","level":4,"score":0.414399117231369},{"id":"https://openalex.org/C147597530","wikidata":"https://www.wikidata.org/wiki/Q369472","display_name":"Computational chemistry","level":1,"score":0.382104754447937},{"id":"https://openalex.org/C161790260","wikidata":"https://www.wikidata.org/wiki/Q82264","display_name":"Catalysis","level":2,"score":0.3092253506183624},{"id":"https://openalex.org/C181199279","wikidata":"https://www.wikidata.org/wiki/Q8047","display_name":"Enzyme","level":2,"score":0.2561805248260498},{"id":"https://openalex.org/C178907741","wikidata":"https://www.wikidata.org/wiki/Q745930","display_name":"Nucleophile","level":3,"score":0.19110041856765747},{"id":"https://openalex.org/C178790620","wikidata":"https://www.wikidata.org/wiki/Q11351","display_name":"Organic chemistry","level":1,"score":0.0906183123588562},{"id":"https://openalex.org/C80161118","wikidata":"https://www.wikidata.org/wiki/Q408520","display_name":"Acetylcholine receptor","level":3,"score":0.07809719443321228},{"id":"https://openalex.org/C170493617","wikidata":"https://www.wikidata.org/wiki/Q208467","display_name":"Receptor","level":2,"score":0.0},{"id":"https://openalex.org/C55493867","wikidata":"https://www.wikidata.org/wiki/Q7094","display_name":"Biochemistry","level":1,"score":0.0}],"mesh":[],"locations_count":2,"locations":[{"id":"doi:10.1021/ja970395v","doi":"https://doi.org/10.1021/ja970395v","is_oa":false,"landing_page_url":"https://doi.org/10.1021/ja970395v","pdf_url":null,"source":{"id":"https://openalex.org/S111155417","display_name":"Journal of the American Chemical Society","issn_l":"0002-7863","issn":["0002-7863","1520-5126","1943-2984"],"is_oa":false,"is_in_doaj":false,"is_core":true,"listed_in":["cwts-core","dongbi-a","jufo-3","ki-jl-3","medline","norway-2","poland-200","russia-white-list-1","vabb-shw"],"host_organization":"https://openalex.org/P4310320006","host_organization_name":"American Chemical Society","host_organization_lineage":["https://openalex.org/P4310320006"],"host_organization_lineage_names":["American Chemical Society"],"type":"journal"},"license":null,"license_id":null,"version":"publishedVersion","is_accepted":true,"is_published":true,"raw_source_name":"Journal of the American Chemical Society","raw_type":"journal-article"},{"id":"pmh:oai:CiteSeerX.psu:10.1.1.27.8973","doi":null,"is_oa":false,"landing_page_url":"http://citeseerx.ist.psu.edu/viewdoc/summary?doi=10.1.1.27.8973","pdf_url":null,"source":null,"license":null,"license_id":null,"version":"submittedVersion","is_accepted":false,"is_published":false,"raw_source_name":"http://planguages.cs.uchicago.edu/www-hpc/tcamc/papers/g199.ps","raw_type":"text"}],"best_oa_location":null,"sustainable_development_goals":[],"study_designs":[],"awards":[],"funders":[],"has_content":{"pdf":false,"grobid_xml":false},"content_urls":null,"referenced_works_count":25,"referenced_works":["https://openalex.org/W1510054038","https://openalex.org/W1518175319","https://openalex.org/W1528949927","https://openalex.org/W1965029170","https://openalex.org/W1969461638","https://openalex.org/W1976734102","https://openalex.org/W2011000826","https://openalex.org/W2015882257","https://openalex.org/W2019252070","https://openalex.org/W2039665613","https://openalex.org/W2040816544","https://openalex.org/W2050083987","https://openalex.org/W2052381633","https://openalex.org/W2063413595","https://openalex.org/W2072739251","https://openalex.org/W2074832474","https://openalex.org/W2079256607","https://openalex.org/W2085958374","https://openalex.org/W2086758152","https://openalex.org/W2112636022","https://openalex.org/W2114621223","https://openalex.org/W2128640429","https://openalex.org/W2156160283","https://openalex.org/W2475718315","https://openalex.org/W4247951394"],"related_works":["https://openalex.org/W1969461638","https://openalex.org/W2065259707","https://openalex.org/W2034040237","https://openalex.org/W2555578427","https://openalex.org/W1994360824","https://openalex.org/W2004549828","https://openalex.org/W2015331537","https://openalex.org/W4255246696","https://openalex.org/W2121140853","https://openalex.org/W4231261028"],"abstract_inverted_index":{"Brownian":[0],"dynamics":[1],"simulations":[2],"of":[3,11,17,46,49,62,77,83,85,103,126,139,148,157,163],"the":[4,8,12,36,44,47,50,63,81,86,90,96,101,104,118,123,127,131,140,144,154,158,164,177,190],"encounter":[5,119],"kinetics":[6],"between":[7],"active":[9,68,106],"site":[10],"wild-type":[13,64,191],"and":[14,65,93,135,167],"Glu199":[15,97],"mutant":[16,67,179],"Torpedo":[18],"californica":[19],"acetylcholinesterase":[20],"(TcAChE)":[21],"with":[22],"a":[23,54,75,112,170,184],"charged":[24],"substrate":[25],"were":[26,40],"performed.":[27],"In":[28],"addition,":[29],"ab":[30],"initio":[31],"quantum":[32,71],"chemical":[33,146],"calculations":[34,72,151],"using":[35,59],"3-21G":[37],"basis":[38],"set":[39],"undertaken":[41],"to":[42,122,183],"probe":[43],"energetics":[45],"transformation":[48],"Michaelis":[51],"complex":[52],"into":[53],"covalently":[55],"bound":[56],"tetrahedral":[57,87,165],"intermediate":[58,88,166],"various":[60],"models":[61],"Glu199Gln":[66,91,178],"sites.":[69],"The":[70],"predicted":[73],"about":[74],"factor":[76],"32":[78],"reduction":[79],"in":[80,100,111,161,176,189],"rate":[82,120],"formation":[84],"upon":[89],"mutation":[92],"showed":[94],"that":[95,169],"residue":[98],"located":[99],"proximity":[102],"enzyme":[105,132],"triad":[107],"boosts":[108],"AChE's":[109],"activity":[110],"dual":[113],"fashion:":[114],"(1)":[115],"by":[116,137],"increasing":[117],"due":[121],"favorable":[124],"modification":[125],"electric":[128],"field":[129],"inside":[130],"reaction":[133],"gorge":[134],"(2)":[136],"stabilization":[138,162],"transition":[141],"state":[142],"for":[143],"first":[145],"step":[147],"catalysis.":[149],"Our":[150],"also":[152],"demonstrate":[153],"critical":[155],"role":[156],"oxyanion":[159],"hole":[160],"suggests":[168],"charge":[171],"relay":[172],"mechanism":[173,187],"may":[174],"operate":[175],"AChE":[180],"as":[181,188],"opposed":[182],"general":[185],"base":[186],"enzyme.":[192]},"counts_by_year":[{"year":2026,"cited_by_count":1},{"year":2020,"cited_by_count":1},{"year":2018,"cited_by_count":1},{"year":2017,"cited_by_count":5},{"year":2015,"cited_by_count":2},{"year":2014,"cited_by_count":3},{"year":2013,"cited_by_count":1},{"year":2012,"cited_by_count":4}],"updated_date":"2026-11-07T11:25:07.637180","created_date":"2016-06-24T00:00:00"}
