{"id":"https://openalex.org/W4368343323","doi":"https://doi.org/10.1021/acs.jcim.3c00127","title":"Nonlocal Effects of Antibiotic-Resistance-Causing Mutations Reveal an Alternative Region for Targeting on FtsW\u2013Penicillin-Binding Protein 3 Complex of <i>Haemophilus influenzae</i>","display_name":"Nonlocal Effects of Antibiotic-Resistance-Causing Mutations Reveal an Alternative Region for Targeting on FtsW\u2013Penicillin-Binding Protein 3 Complex of <i>Haemophilus influenzae</i>","publication_year":2023,"publication_date":"2023-05-04","ids":{"openalex":"https://openalex.org/W4368343323","doi":"https://doi.org/10.1021/acs.jcim.3c00127","pmid":"https://pubmed.ncbi.nlm.nih.gov/37141552"},"language":"en","primary_location":{"id":"doi:10.1021/acs.jcim.3c00127","is_oa":false,"landing_page_url":"https://doi.org/10.1021/acs.jcim.3c00127","pdf_url":null,"source":{"id":"https://openalex.org/S167262187","display_name":"Journal of Chemical Information and Modeling","issn_l":"1549-9596","issn":["1549-9596","1549-960X"],"is_oa":false,"is_in_doaj":false,"is_core":true,"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 Chemical Information and Modeling","raw_type":"journal-article"},"type":"article","indexed_in":["crossref","pubmed"],"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/A5091313653","display_name":"Almotasem Belah Alhamwi","orcid":"https://orcid.org/0009-0009-1404-5107"},"institutions":[{"id":"https://openalex.org/I3125470973","display_name":"Istanbul Medipol University","ror":"https://ror.org/037jwzz50","country_code":"TR","type":"education","lineage":["https://openalex.org/I3125470973"]}],"countries":["TR"],"is_corresponding":false,"raw_author_name":"Almotasem Belah Alhamwi","raw_affiliation_strings":["Graduate School of Engineering and Natural Sciences, Istanbul Medipol University, 34810 Istanbul, Turkey"],"affiliations":[{"raw_affiliation_string":"Graduate School of Engineering and Natural Sciences, Istanbul Medipol University, 34810 Istanbul, Turkey","institution_ids":["https://openalex.org/I3125470973"]}]},{"author_position":"middle","author":{"id":"https://openalex.org/A5054767162","display_name":"Canan At\u0131lgan","orcid":"https://orcid.org/0000-0003-0557-6044"},"institutions":[{"id":"https://openalex.org/I134235054","display_name":"Sabanc\u0131 \u00dcniversitesi","ror":"https://ror.org/049asqa32","country_code":"TR","type":"education","lineage":["https://openalex.org/I134235054"]}],"countries":["TR"],"is_corresponding":false,"raw_author_name":"Canan Atilgan","raw_affiliation_strings":["Faculty of Engineering and Natural Sciences, Sabanci University, 34956 Istanbul, Turkey"],"affiliations":[{"raw_affiliation_string":"Faculty of Engineering and Natural Sciences, Sabanci University, 34956 Istanbul, Turkey","institution_ids":["https://openalex.org/I134235054"]}]},{"author_position":"last","author":{"id":"https://openalex.org/A5057659093","display_name":"\u00d6zge \u015eensoy","orcid":"https://orcid.org/0000-0001-5950-3436"},"institutions":[{"id":"https://openalex.org/I3125470973","display_name":"Istanbul Medipol University","ror":"https://ror.org/037jwzz50","country_code":"TR","type":"education","lineage":["https://openalex.org/I3125470973"]}],"countries":["TR"],"is_corresponding":true,"raw_author_name":"Ozge Sensoy","raw_affiliation_strings":["Graduate School of Engineering and Natural Sciences, Istanbul Medipol University, 34810 Istanbul, Turkey","Regenerative and Restorative Medicine Research Center (REMER), Research Institute for Health Sciences and Technologies (SABITA), Istanbul Medipol University, 34810 Istanbul, Turkey"],"affiliations":[{"raw_affiliation_string":"Graduate School of Engineering and Natural Sciences, Istanbul Medipol University, 34810 Istanbul, Turkey","institution_ids":["https://openalex.org/I3125470973"]},{"raw_affiliation_string":"Regenerative and Restorative Medicine Research Center (REMER), Research Institute for Health Sciences and Technologies (SABITA), Istanbul Medipol University, 34810 Istanbul, Turkey","institution_ids":["https://openalex.org/I3125470973"]}]}],"institutions":[],"countries_distinct_count":1,"institutions_distinct_count":3,"corresponding_author_ids":["https://openalex.org/A5057659093"],"corresponding_institution_ids":["https://openalex.org/I3125470973"],"apc_list":null,"apc_paid":null,"fwci":0.3185,"has_fulltext":false,"cited_by_count":2,"citation_normalized_percentile":{"value":0.62764287,"is_in_top_1_percent":false,"is_in_top_10_percent":false},"cited_by_percentile_year":{"min":94,"max":96},"biblio":{"volume":"63","issue":"10","first_page":"3094","last_page":"3104"},"is_retracted":false,"is_paratext":false,"is_xpac":false,"primary_topic":{"id":"https://openalex.org/T10521","display_name":"RNA and protein synthesis mechanisms","score":0.9998000264167786,"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"}},"topics":[{"id":"https://openalex.org/T10521","display_name":"RNA and protein synthesis mechanisms","score":0.9998000264167786,"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"}},{"id":"https://openalex.org/T10120","display_name":"Bacterial Genetics and Biotechnology","score":0.9984999895095825,"subfield":{"id":"https://openalex.org/subfields/1311","display_name":"Genetics"},"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"}},{"id":"https://openalex.org/T11016","display_name":"Monoclonal and Polyclonal Antibodies Research","score":0.9975000023841858,"subfield":{"id":"https://openalex.org/subfields/2741","display_name":"Radiology, Nuclear Medicine and Imaging"},"field":{"id":"https://openalex.org/fields/27","display_name":"Medicine"},"domain":{"id":"https://openalex.org/domains/4","display_name":"Health Sciences"}}],"keywords":[{"id":"https://openalex.org/keywords/penicillin-binding-proteins","display_name":"Penicillin binding proteins","score":0.806144654750824},{"id":"https://openalex.org/keywords/haemophilus-influenzae","display_name":"Haemophilus influenzae","score":0.7968053817749023},{"id":"https://openalex.org/keywords/antibiotics","display_name":"Antibiotics","score":0.6476609110832214},{"id":"https://openalex.org/keywords/microbiology","display_name":"Microbiology","score":0.6391887664794922},{"id":"https://openalex.org/keywords/penicillin","display_name":"Penicillin","score":0.6306422352790833},{"id":"https://openalex.org/keywords/penicillin-resistance","display_name":"Penicillin resistance","score":0.5529451966285706},{"id":"https://openalex.org/keywords/antibiotic-resistance","display_name":"Antibiotic resistance","score":0.547161877155304},{"id":"https://openalex.org/keywords/haemophilus","display_name":"Haemophilus","score":0.45367664098739624},{"id":"https://openalex.org/keywords/mutation","display_name":"Mutation","score":0.4532703757286072},{"id":"https://openalex.org/keywords/biology","display_name":"Biology","score":0.3982711434364319},{"id":"https://openalex.org/keywords/genetics","display_name":"Genetics","score":0.3923434317111969},{"id":"https://openalex.org/keywords/computational-biology","display_name":"Computational biology","score":0.3467199206352234},{"id":"https://openalex.org/keywords/chemistry","display_name":"Chemistry","score":0.32451754808425903},{"id":"https://openalex.org/keywords/bacteria","display_name":"Bacteria","score":0.24424222111701965},{"id":"https://openalex.org/keywords/gene","display_name":"Gene","score":0.14210766553878784}],"concepts":[{"id":"https://openalex.org/C2776653525","wikidata":"https://www.wikidata.org/wiki/Q7162855","display_name":"Penicillin binding proteins","level":4,"score":0.806144654750824},{"id":"https://openalex.org/C2776925733","wikidata":"https://www.wikidata.org/wiki/Q1141979","display_name":"Haemophilus influenzae","level":3,"score":0.7968053817749023},{"id":"https://openalex.org/C501593827","wikidata":"https://www.wikidata.org/wiki/Q12187","display_name":"Antibiotics","level":2,"score":0.6476609110832214},{"id":"https://openalex.org/C89423630","wikidata":"https://www.wikidata.org/wiki/Q7193","display_name":"Microbiology","level":1,"score":0.6391887664794922},{"id":"https://openalex.org/C174802600","wikidata":"https://www.wikidata.org/wiki/Q12190","display_name":"Penicillin","level":3,"score":0.6306422352790833},{"id":"https://openalex.org/C3019450489","wikidata":"https://www.wikidata.org/wiki/Q12190","display_name":"Penicillin resistance","level":4,"score":0.5529451966285706},{"id":"https://openalex.org/C94665300","wikidata":"https://www.wikidata.org/wiki/Q63391344","display_name":"Antibiotic resistance","level":3,"score":0.547161877155304},{"id":"https://openalex.org/C2776402342","wikidata":"https://www.wikidata.org/wiki/Q311275","display_name":"Haemophilus","level":3,"score":0.45367664098739624},{"id":"https://openalex.org/C501734568","wikidata":"https://www.wikidata.org/wiki/Q42918","display_name":"Mutation","level":3,"score":0.4532703757286072},{"id":"https://openalex.org/C86803240","wikidata":"https://www.wikidata.org/wiki/Q420","display_name":"Biology","level":0,"score":0.3982711434364319},{"id":"https://openalex.org/C54355233","wikidata":"https://www.wikidata.org/wiki/Q7162","display_name":"Genetics","level":1,"score":0.3923434317111969},{"id":"https://openalex.org/C70721500","wikidata":"https://www.wikidata.org/wiki/Q177005","display_name":"Computational biology","level":1,"score":0.3467199206352234},{"id":"https://openalex.org/C185592680","wikidata":"https://www.wikidata.org/wiki/Q2329","display_name":"Chemistry","level":0,"score":0.32451754808425903},{"id":"https://openalex.org/C523546767","wikidata":"https://www.wikidata.org/wiki/Q10876","display_name":"Bacteria","level":2,"score":0.24424222111701965},{"id":"https://openalex.org/C104317684","wikidata":"https://www.wikidata.org/wiki/Q7187","display_name":"Gene","level":2,"score":0.14210766553878784}],"mesh":[{"descriptor_ui":"D000900","descriptor_name":"Anti-Bacterial Agents","qualifier_ui":"Q000494","qualifier_name":"pharmacology","is_major_topic":true},{"descriptor_ui":"D000900","descriptor_name":"Anti-Bacterial Agents","qualifier_ui":"Q000494","qualifier_name":"pharmacology","is_major_topic":true},{"descriptor_ui":"D000900","descriptor_name":"Anti-Bacterial Agents","qualifier_ui":"Q000494","qualifier_name":"pharmacology","is_major_topic":true},{"descriptor_ui":"D006193","descriptor_name":"Haemophilus influenzae","qualifier_ui":"Q000235","qualifier_name":"genetics","is_major_topic":true},{"descriptor_ui":"D006193","descriptor_name":"Haemophilus influenzae","qualifier_ui":"Q000235","qualifier_name":"genetics","is_major_topic":true},{"descriptor_ui":"D006193","descriptor_name":"Haemophilus influenzae","qualifier_ui":"Q000235","qualifier_name":"genetics","is_major_topic":true},{"descriptor_ui":"D008826","descriptor_name":"Microbial Sensitivity Tests","qualifier_ui":null,"qualifier_name":null,"is_major_topic":false},{"descriptor_ui":"D008826","descriptor_name":"Microbial Sensitivity Tests","qualifier_ui":null,"qualifier_name":null,"is_major_topic":false},{"descriptor_ui":"D008826","descriptor_name":"Microbial Sensitivity Tests","qualifier_ui":null,"qualifier_name":null,"is_major_topic":false},{"descriptor_ui":"D009154","descriptor_name":"Mutation","qualifier_ui":null,"qualifier_name":null,"is_major_topic":false},{"descriptor_ui":"D009154","descriptor_name":"Mutation","qualifier_ui":null,"qualifier_name":null,"is_major_topic":false},{"descriptor_ui":"D009154","descriptor_name":"Mutation","qualifier_ui":null,"qualifier_name":null,"is_major_topic":false},{"descriptor_ui":"D046915","descriptor_name":"Penicillin-Binding Proteins","qualifier_ui":"Q000235","qualifier_name":"genetics","is_major_topic":false},{"descriptor_ui":"D046915","descriptor_name":"Penicillin-Binding Proteins","qualifier_ui":"Q000235","qualifier_name":"genetics","is_major_topic":false},{"descriptor_ui":"D046915","descriptor_name":"Penicillin-Binding Proteins","qualifier_ui":"Q000235","qualifier_name":"genetics","is_major_topic":false},{"descriptor_ui":"D046915","descriptor_name":"Penicillin-Binding Proteins","qualifier_ui":"Q000378","qualifier_name":"metabolism","is_major_topic":false},{"descriptor_ui":"D046915","descriptor_name":"Penicillin-Binding Proteins","qualifier_ui":"Q000378","qualifier_name":"metabolism","is_major_topic":false},{"descriptor_ui":"D046915","descriptor_name":"Penicillin-Binding Proteins","qualifier_ui":"Q000378","qualifier_name":"metabolism","is_major_topic":false},{"descriptor_ui":"D046915","descriptor_name":"Penicillin-Binding Proteins","qualifier_ui":"Q000494","qualifier_name":"pharmacology","is_major_topic":false},{"descriptor_ui":"D046915","descriptor_name":"Penicillin-Binding Proteins","qualifier_ui":"Q000494","qualifier_name":"pharmacology","is_major_topic":false},{"descriptor_ui":"D046915","descriptor_name":"Penicillin-Binding Proteins","qualifier_ui":"Q000494","qualifier_name":"pharmacology","is_major_topic":false},{"descriptor_ui":"D047090","descriptor_name":"beta-Lactams","qualifier_ui":null,"qualifier_name":null,"is_major_topic":false},{"descriptor_ui":"D047090","descriptor_name":"beta-Lactams","qualifier_ui":null,"qualifier_name":null,"is_major_topic":false},{"descriptor_ui":"D047090","descriptor_name":"beta-Lactams","qualifier_ui":null,"qualifier_name":null,"is_major_topic":false}],"locations_count":2,"locations":[{"id":"doi:10.1021/acs.jcim.3c00127","is_oa":false,"landing_page_url":"https://doi.org/10.1021/acs.jcim.3c00127","pdf_url":null,"source":{"id":"https://openalex.org/S167262187","display_name":"Journal of Chemical Information and Modeling","issn_l":"1549-9596","issn":["1549-9596","1549-960X"],"is_oa":false,"is_in_doaj":false,"is_core":true,"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 Chemical Information and Modeling","raw_type":"journal-article"},{"id":"pmid:37141552","is_oa":false,"landing_page_url":"https://pubmed.ncbi.nlm.nih.gov/37141552","pdf_url":null,"source":{"id":"https://openalex.org/S4306525036","display_name":"PubMed","issn_l":null,"issn":null,"is_oa":false,"is_in_doaj":false,"is_core":false,"host_organization":"https://openalex.org/I1299303238","host_organization_name":"National Institutes of Health","host_organization_lineage":["https://openalex.org/I1299303238"],"host_organization_lineage_names":[],"type":"repository"},"license":null,"license_id":null,"version":"publishedVersion","is_accepted":true,"is_published":true,"raw_source_name":"Journal of chemical information and modeling","raw_type":null}],"best_oa_location":null,"sustainable_development_goals":[{"display_name":"Good health and well-being","id":"https://metadata.un.org/sdg/3","score":0.6000000238418579}],"awards":[],"funders":[],"has_content":{"pdf":false,"grobid_xml":false},"content_urls":null,"referenced_works_count":43,"referenced_works":["https://openalex.org/W1031578623","https://openalex.org/W1979658584","https://openalex.org/W1995770177","https://openalex.org/W2029068615","https://openalex.org/W2029667189","https://openalex.org/W2031168104","https://openalex.org/W2035800315","https://openalex.org/W2045587278","https://openalex.org/W2052779789","https://openalex.org/W2073765675","https://openalex.org/W2087773092","https://openalex.org/W2103691419","https://openalex.org/W2105999876","https://openalex.org/W2109793735","https://openalex.org/W2116007609","https://openalex.org/W2119267663","https://openalex.org/W2119877522","https://openalex.org/W2130479394","https://openalex.org/W2142532813","https://openalex.org/W2160544821","https://openalex.org/W2283716387","https://openalex.org/W2314292783","https://openalex.org/W2460255279","https://openalex.org/W2573959761","https://openalex.org/W2743526077","https://openalex.org/W2757576334","https://openalex.org/W2951966558","https://openalex.org/W2960403291","https://openalex.org/W2964360532","https://openalex.org/W2965630387","https://openalex.org/W2989135569","https://openalex.org/W2997234557","https://openalex.org/W2999866742","https://openalex.org/W3012262711","https://openalex.org/W3024551994","https://openalex.org/W3046878556","https://openalex.org/W3087318638","https://openalex.org/W3097145107","https://openalex.org/W3153879570","https://openalex.org/W3160393722","https://openalex.org/W3189652744","https://openalex.org/W3197665808","https://openalex.org/W3210500140"],"related_works":["https://openalex.org/W2386345146","https://openalex.org/W1986889155","https://openalex.org/W4247831171","https://openalex.org/W1522784025","https://openalex.org/W1979424193","https://openalex.org/W2418669643","https://openalex.org/W2395116299","https://openalex.org/W2091078308","https://openalex.org/W1852497695","https://openalex.org/W1991833505"],"abstract_inverted_index":{"Currently":[0],"prescribed":[1],"antibiotics":[2],"target":[3],"the":[4,21,26,39,42,51,64,105,107,110,114,122,128,133,136,141,144,148,156,159,167,170,175,182,194,202,206,213,233,242],"catalytic":[5,123],"sites":[6,32],"of":[7,23,28,38,41,53,66,104,109,117,135,143,158,169,189,236,244],"wild-type":[8,176],"bacterial":[9],"proteins;":[10],"however,":[11],"bacteria":[12],"adopt":[13],"mutations":[14,96],"at":[15],"this":[16],"site,":[17],"eventually":[18],"leading":[19],"to":[20,49,127,191,201,241,248],"emergence":[22],"resistance.":[24],"Therefore,":[25],"identification":[27],"alternative":[29],"drug":[30],"binding":[31,220],"is":[33],"crucial,":[34],"which":[35,87,112,139],"requires":[36],"knowledge":[37],"dynamics":[40,65,157],"mutant":[43,149,178,207,237],"protein.":[44],"Here,":[45],"we":[46,210],"set":[47],"out":[48],"investigate":[50],"impact":[52],"a":[54,67,186],"high-resistance-causing":[55],"triple":[56],"mutation":[57],"(S385T":[58],"+":[59,61],"L389F":[60],"N526K)":[62],"on":[63],"prioritized":[68],"resistant":[69,250],"pathogen,":[70],"<i>Haemophilus":[71],"influenzae</i>,":[72],"using":[73],"computational":[74],"techniques.":[75],"We":[76,93,180],"studied":[77],"penicillin-binding":[78],"protein":[79],"3":[80],"(PBP3)":[81],"and":[82,99,121,177],"its":[83],"complex":[84],"with":[85,221],"FtsW,":[86],"display":[88],"resistance":[89],"toward":[90],"\u03b2-lactam":[91,222],"antibiotics.":[92],"showed":[94,181],"that":[95,212,227,230],"displayed":[97],"local":[98],"nonlocal":[100,154],"effects.":[101],"In":[102,131],"terms":[103],"former,":[106],"orientation":[108],"\u03b2-sheet,":[111],"surrounds":[113],"active":[115],"site":[116,124],"PBP3,":[118],"was":[119,125,172],"impacted":[120],"exposed":[126],"periplasmic":[129,163],"region.":[130],"addition,":[132],"flexibility":[134],"\u03b23-\u03b24":[137],"loop,":[138],"modulates":[140],"catalysis":[142],"enzyme,":[145],"increased":[146],"in":[147,193,205,217],"FtsW-PBP3":[150],"complex.":[151],"As":[152],"for":[153],"effects,":[155],"pedestal":[160],"domain":[161,204],"(N-terminal":[162],"modulus":[164],"(N-t)),":[165],"i.e.,":[166],"opening":[168],"fork,":[171],"different":[173],"between":[174],"enzymes.":[179],"closed":[183,214,234],"fork":[184,215,235],"caused":[185],"greater":[187],"number":[188],"residues":[190],"participate":[192],"hypothesized":[195],"allosteric":[196],"communication":[197],"network":[198],"connecting":[199],"N-t":[200],"transpeptidase":[203],"enzyme.":[208],"Finally,":[209],"demonstrated":[211],"results":[216],"more":[218,245],"favorable":[219],"antibiotics,":[223],"particularly":[224],"cefixime,":[225],"suggesting":[226],"small":[228],"therapeutics":[229],"can":[231],"stabilize":[232],"PBP3":[238],"may":[239],"lead":[240],"development":[243],"effective":[246],"molecules":[247],"combat":[249],"bacteria.":[251]},"counts_by_year":[{"year":2024,"cited_by_count":2}],"updated_date":"2025-11-06T03:46:38.306776","created_date":"2025-10-10T00:00:00"}