{"id":"https://openalex.org/W65967812","doi":null,"title":"Mutational Analysis and Redesign of Alpha-class Glutathione Transferases for Enhanced Azathioprine Activity","display_name":"Mutational Analysis and Redesign of Alpha-class Glutathione Transferases for Enhanced Azathioprine Activity","publication_year":2013,"publication_date":"2013-01-01","ids":{"openalex":"https://openalex.org/W65967812","mag":"65967812"},"language":"en","primary_location":{"id":"pmh:oai:DiVA.org:uu-167332","doi":null,"is_oa":true,"landing_page_url":"http://urn.kb.se/resolve?urn=urn:nbn:se:uu:diva-167332","pdf_url":null,"source":{"id":"https://openalex.org/S4306401559","display_name":"KTH Publication Database DiVA (KTH Royal Institute of Technology)","issn_l":null,"issn":null,"is_oa":false,"is_in_doaj":false,"is_core":false,"listed_in":[],"host_organization":"https://openalex.org/I86987016","host_organization_name":"KTH Royal Institute of Technology","host_organization_lineage":["https://openalex.org/I86987016"],"host_organization_lineage_names":[],"type":"repository"},"license":"other-oa","license_id":"https://openalex.org/licenses/other-oa","version":"submittedVersion","is_accepted":false,"is_published":false,"raw_source_name":null,"raw_type":"info:eu-repo/semantics/doctoralThesis"},"volume":null,"type":"dissertation","is_traditional":true,"indexed_in":[],"open_access":{"is_oa":true,"oa_status":"green","oa_url":"http://urn.kb.se/resolve?urn=urn:nbn:se:uu:diva-167332","any_repository_has_fulltext":true},"authorships":[{"author_position":"first","author":{"id":"https://openalex.org/A5062499746","display_name":"Olof Mod\u00e9n","orcid":null,"observed_orcids":[]},"institutions":[],"countries":[],"is_corresponding":true,"raw_author_name":"Olof Mod\u00e9n","raw_affiliation_strings":[],"raw_orcid":null,"affiliations":[]}],"institutions":[],"countries_distinct_count":0,"institutions_distinct_count":0,"corresponding_author_ids":["https://openalex.org/A5062499746"],"corresponding_institution_ids":[],"apc_list":null,"apc_paid":null,"fwci":null,"has_fulltext":false,"cited_by_count":1,"citation_normalized_percentile":null,"cited_by_percentile_year":null,"biblio":{"volume":null,"issue":null,"first_page":null,"last_page":null},"is_retracted":false,"is_paratext":false,"is_xpac":false,"primary_topic":{"id":"https://openalex.org/T12187","display_name":"Glutathione Transferases and Polymorphisms","score":0.9990000128746033,"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/T12187","display_name":"Glutathione Transferases and Polymorphisms","score":0.9990000128746033,"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/T10375","display_name":"Pharmacogenetics and Drug Metabolism","score":0.000699999975040555,"subfield":{"id":"https://openalex.org/subfields/3004","display_name":"Pharmacology"},"field":{"id":"https://openalex.org/fields/30","display_name":"Pharmacology, Toxicology and Pharmaceutics"},"domain":{"id":"https://openalex.org/domains/1","display_name":"Life Sciences"}},{"id":"https://openalex.org/T10404","display_name":"Enzyme Catalysis and Immobilization","score":0.0,"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/glutathione-s-transferase-a2","display_name":"glutathione S-transferase A2","score":0.8519999980926514},{"id":"https://openalex.org/keywords/prodrug-activation","display_name":"prodrug activation","score":0.6349999904632568},{"id":"https://openalex.org/keywords/enzyme-mutagenesis","display_name":"enzyme mutagenesis","score":0.5509999990463257},{"id":"https://openalex.org/keywords/dna-shuffling","display_name":"DNA shuffling","score":0.6869999766349792},{"id":"https://openalex.org/keywords/catalytic-efficiency","display_name":"catalytic efficiency","score":0.7260000109672546},{"id":"https://openalex.org/keywords/inflammatory-bowel-disease","display_name":"inflammatory bowel disease","score":0.753000020980835},{"id":"https://openalex.org/keywords/adverse-drug-reactions","display_name":"adverse drug reactions","score":0.671999990940094},{"id":"https://openalex.org/keywords/enzyme-redesign","display_name":"enzyme redesign","score":0.5090000033378601},{"id":"https://openalex.org/keywords/enzyme-prodrug-therapy","display_name":"enzyme prodrug therapy","score":0.7009999752044678},{"id":"https://openalex.org/keywords/structure-function-relationship","display_name":"structure-function relationship","score":0.7099999785423279}],"concepts":[{"id":"https://openalex.org/C2777212361","wikidata":"https://www.wikidata.org/wiki/Q5127848","display_name":"Class (philosophy)","level":2,"score":0.5421380400657654},{"id":"https://openalex.org/C64943373","wikidata":"https://www.wikidata.org/wiki/Q2651003","display_name":"Alpha (finance)","level":4,"score":0.4734370708465576},{"id":"https://openalex.org/C54355233","wikidata":"https://www.wikidata.org/wiki/Q7162","display_name":"Genetics","level":1,"score":0.4518366754055023},{"id":"https://openalex.org/C2776760755","wikidata":"https://www.wikidata.org/wiki/Q18939","display_name":"Azathioprine","level":3,"score":0.4415869414806366},{"id":"https://openalex.org/C538909803","wikidata":"https://www.wikidata.org/wiki/Q116907","display_name":"Glutathione","level":3,"score":0.42487239837646484},{"id":"https://openalex.org/C185592680","wikidata":"https://www.wikidata.org/wiki/Q2329","display_name":"Chemistry","level":0,"score":0.3854528069496155},{"id":"https://openalex.org/C86803240","wikidata":"https://www.wikidata.org/wiki/Q420","display_name":"Biology","level":0,"score":0.3840849697589874},{"id":"https://openalex.org/C70721500","wikidata":"https://www.wikidata.org/wiki/Q177005","display_name":"Computational biology","level":1,"score":0.3765450119972229},{"id":"https://openalex.org/C55493867","wikidata":"https://www.wikidata.org/wiki/Q7094","display_name":"Biochemistry","level":1,"score":0.30878493189811707},{"id":"https://openalex.org/C41008148","wikidata":"https://www.wikidata.org/wiki/Q21198","display_name":"Computer science","level":0,"score":0.25573140382766724},{"id":"https://openalex.org/C33923547","wikidata":"https://www.wikidata.org/wiki/Q395","display_name":"Mathematics","level":0,"score":0.17632132768630981},{"id":"https://openalex.org/C181199279","wikidata":"https://www.wikidata.org/wiki/Q8047","display_name":"Enzyme","level":2,"score":0.1698509156703949},{"id":"https://openalex.org/C71924100","wikidata":"https://www.wikidata.org/wiki/Q11190","display_name":"Medicine","level":0,"score":0.16344401240348816},{"id":"https://openalex.org/C154945302","wikidata":"https://www.wikidata.org/wiki/Q11660","display_name":"Artificial intelligence","level":1,"score":0.1497858762741089},{"id":"https://openalex.org/C126322002","wikidata":"https://www.wikidata.org/wiki/Q11180","display_name":"Internal medicine","level":1,"score":0.12800520658493042},{"id":"https://openalex.org/C105795698","wikidata":"https://www.wikidata.org/wiki/Q12483","display_name":"Statistics","level":1,"score":0.11136209964752197},{"id":"https://openalex.org/C171606756","wikidata":"https://www.wikidata.org/wiki/Q506132","display_name":"Psychometrics","level":2,"score":0.0},{"id":"https://openalex.org/C49453240","wikidata":"https://www.wikidata.org/wiki/Q1592163","display_name":"Construct validity","level":3,"score":0.0},{"id":"https://openalex.org/C2779134260","wikidata":"https://www.wikidata.org/wiki/Q12136","display_name":"Disease","level":2,"score":0.0}],"mesh":[],"locations_count":2,"locations":[{"id":"pmh:oai:DiVA.org:uu-167332","doi":null,"is_oa":true,"landing_page_url":"http://urn.kb.se/resolve?urn=urn:nbn:se:uu:diva-167332","pdf_url":null,"source":{"id":"https://openalex.org/S4306401559","display_name":"KTH Publication Database DiVA (KTH Royal Institute of Technology)","issn_l":null,"issn":null,"is_oa":false,"is_in_doaj":false,"is_core":false,"listed_in":[],"host_organization":"https://openalex.org/I86987016","host_organization_name":"KTH Royal Institute of Technology","host_organization_lineage":["https://openalex.org/I86987016"],"host_organization_lineage_names":[],"type":"repository"},"license":"other-oa","license_id":"https://openalex.org/licenses/other-oa","version":"submittedVersion","is_accepted":false,"is_published":false,"raw_source_name":null,"raw_type":"info:eu-repo/semantics/doctoralThesis"},{"id":"mag:65967812","doi":null,"is_oa":false,"landing_page_url":"https://uu.diva-portal.org/smash/get/diva2:619112/FULLTEXT01.pdf","pdf_url":null,"source":null,"license":null,"license_id":null,"version":null,"is_accepted":false,"is_published":false,"raw_source_name":null,"raw_type":null}],"best_oa_location":{"id":"pmh:oai:DiVA.org:uu-167332","doi":null,"is_oa":true,"landing_page_url":"http://urn.kb.se/resolve?urn=urn:nbn:se:uu:diva-167332","pdf_url":null,"source":{"id":"https://openalex.org/S4306401559","display_name":"KTH Publication Database DiVA (KTH Royal Institute of Technology)","issn_l":null,"issn":null,"is_oa":false,"is_in_doaj":false,"is_core":false,"listed_in":[],"host_organization":"https://openalex.org/I86987016","host_organization_name":"KTH Royal Institute of Technology","host_organization_lineage":["https://openalex.org/I86987016"],"host_organization_lineage_names":[],"type":"repository"},"license":"other-oa","license_id":"https://openalex.org/licenses/other-oa","version":"submittedVersion","is_accepted":false,"is_published":false,"raw_source_name":null,"raw_type":"info:eu-repo/semantics/doctoralThesis"},"sustainable_development_goals":[{"id":"https://metadata.un.org/sdg/3","display_name":"Good health and well-being","score":0.8371999859809875}],"study_designs":[],"awards":[],"funders":[],"has_content":{"pdf":false,"grobid_xml":false},"content_urls":null,"referenced_works_count":156,"referenced_works":["https://openalex.org/W66995464","https://openalex.org/W141364591","https://openalex.org/W630005112","https://openalex.org/W1481475489","https://openalex.org/W1511937926","https://openalex.org/W1519895850","https://openalex.org/W1534517380","https://openalex.org/W1538865925","https://openalex.org/W1553784037","https://openalex.org/W1584851347","https://openalex.org/W1594684968","https://openalex.org/W1788236687","https://openalex.org/W1868880553","https://openalex.org/W1869465538","https://openalex.org/W1891701788","https://openalex.org/W1912583595","https://openalex.org/W1919048035","https://openalex.org/W1962090536","https://openalex.org/W1965804472","https://openalex.org/W1966656991","https://openalex.org/W1971523253","https://openalex.org/W1972785852","https://openalex.org/W1973067363","https://openalex.org/W1973123086","https://openalex.org/W1973910453","https://openalex.org/W1974292630","https://openalex.org/W1976547627","https://openalex.org/W1977903334","https://openalex.org/W1979860927","https://openalex.org/W1981793850","https://openalex.org/W1983528535","https://openalex.org/W1983794592","https://openalex.org/W1984690893","https://openalex.org/W1985349154","https://openalex.org/W1987010560","https://openalex.org/W1987703405","https://openalex.org/W1991619620","https://openalex.org/W1992295599","https://openalex.org/W1993575340","https://openalex.org/W1995855419","https://openalex.org/W1996409190","https://openalex.org/W1997646259","https://openalex.org/W1997999969","https://openalex.org/W1998003752","https://openalex.org/W1998980013","https://openalex.org/W1999104032","https://openalex.org/W2000340331","https://openalex.org/W2001587962","https://openalex.org/W2001786662","https://openalex.org/W2001952758","https://openalex.org/W2003414176","https://openalex.org/W2003470884","https://openalex.org/W2004408262","https://openalex.org/W2004807236","https://openalex.org/W2008753966","https://openalex.org/W2010649076","https://openalex.org/W2011513747","https://openalex.org/W2014513936","https://openalex.org/W2017474351","https://openalex.org/W2019124696","https://openalex.org/W2019732623","https://openalex.org/W2020746850","https://openalex.org/W2022388400","https://openalex.org/W2022453066","https://openalex.org/W2023214895","https://openalex.org/W2024293518","https://openalex.org/W2025101573","https://openalex.org/W2025882541","https://openalex.org/W2026301529","https://openalex.org/W2028493269","https://openalex.org/W2032476057","https://openalex.org/W2032679861","https://openalex.org/W2033702490","https://openalex.org/W2034422333","https://openalex.org/W2035029116","https://openalex.org/W2037532093","https://openalex.org/W2040728839","https://openalex.org/W2041051867","https://openalex.org/W2042527315","https://openalex.org/W2043844484","https://openalex.org/W2047015012","https://openalex.org/W2053242463","https://openalex.org/W2054172648","https://openalex.org/W2054782645","https://openalex.org/W2057029503","https://openalex.org/W2059143808","https://openalex.org/W2060918019","https://openalex.org/W2061120504","https://openalex.org/W2063668143","https://openalex.org/W2066381187","https://openalex.org/W2072740462","https://openalex.org/W2073590852","https://openalex.org/W2074588113","https://openalex.org/W2075157068","https://openalex.org/W2077771104","https://openalex.org/W2079866488","https://openalex.org/W2079943300","https://openalex.org/W2083446995","https://openalex.org/W2084802783","https://openalex.org/W2086462671","https://openalex.org/W2086721113","https://openalex.org/W2087479173","https://openalex.org/W2088875951","https://openalex.org/W2090923092","https://openalex.org/W2099560117","https://openalex.org/W2100942700","https://openalex.org/W2102242005","https://openalex.org/W2102549899","https://openalex.org/W2106861615","https://openalex.org/W2107105699","https://openalex.org/W2112299788","https://openalex.org/W2113340032","https://openalex.org/W2114806957","https://openalex.org/W2119665774","https://openalex.org/W2120560574","https://openalex.org/W2122491264","https://openalex.org/W2122602670","https://openalex.org/W2125136235","https://openalex.org/W2126840368","https://openalex.org/W2127797433","https://openalex.org/W2128964327","https://openalex.org/W2131683781","https://openalex.org/W2132206609","https://openalex.org/W2133556852","https://openalex.org/W2133701300","https://openalex.org/W2134450909","https://openalex.org/W2135621366","https://openalex.org/W2135958206","https://openalex.org/W2136628679","https://openalex.org/W2136913776","https://openalex.org/W2140877639","https://openalex.org/W2145648574","https://openalex.org/W2146179914","https://openalex.org/W2148127987","https://openalex.org/W2148612893","https://openalex.org/W2150460043","https://openalex.org/W2151601961","https://openalex.org/W2153052535","https://openalex.org/W2153190211","https://openalex.org/W2154011738","https://openalex.org/W2155095892","https://openalex.org/W2156624967","https://openalex.org/W2157836140","https://openalex.org/W2158418636","https://openalex.org/W2158815442","https://openalex.org/W2160253662","https://openalex.org/W2160294964","https://openalex.org/W2166022522","https://openalex.org/W2167915961","https://openalex.org/W2171155058","https://openalex.org/W2171682368","https://openalex.org/W2397467576","https://openalex.org/W2413931281","https://openalex.org/W2417082956","https://openalex.org/W3025531431","https://openalex.org/W4365786846"],"related_works":["https://openalex.org/W1596210849","https://openalex.org/W2142489871","https://openalex.org/W2007318896","https://openalex.org/W2055724556","https://openalex.org/W2076117076","https://openalex.org/W2090707550","https://openalex.org/W2596308851","https://openalex.org/W2126840368","https://openalex.org/W2060877740","https://openalex.org/W562393570"],"abstract_inverted_index":{"Glutathione":[0],"transferase":[1],"(GST)":[2],"A2-2":[3,144],"is":[4,105,182],"the":[5,19,44,51,76,125,130,164,212,238,258,273,289],"human":[6,143],"enzyme":[7],"most":[8,45,203],"efficient":[9],"in":[10,97,112,211,244,261,296],"catalyzing":[11],"azathioprine":[12,65,73,104,190,259,286],"activation.":[13],"Structure-function":[14],"relationships":[15],"were":[16,38,41,91,95,145],"sought":[17],"explaining":[18],"higher":[20,64,152],"catalytic":[21,153,221,283],"efficiency":[22,154,222,284],"compared":[23,287],"to":[24,71,80,118,158,163,170,288],"other":[25,89],"alpha":[26,262],"class":[27,263],"GSTs.":[28],"By":[29],"screening":[30],"a":[31,159,192,218,233,245],"DNA":[32],"shuffling":[33],"library,":[34],"five":[35],"recombined":[36],"segments":[37,56,83],"identified":[39],"that":[40,237],"conserved":[42,82],"among":[43],"active":[46,204],"mutants.":[47],"Mutational":[48],"analysis":[49,253],"confirmed":[50],"importance":[52],"of":[53,124,129,137,142,180,189,195,226,257],"these":[54,81,138],"short":[55],"as":[57,268],"their":[58],"insertion":[59],"into":[60,191],"low-active":[61],"GSTs":[62,181,264],"introduced":[63],"activity.":[66],"Besides,":[67],"H-site":[68],"mutagenesis":[69],"led":[70],"decreased":[72],"activity":[74,87],"when":[75,88],"targeted":[77,297],"positions":[78,90,98,199],"belonged":[79],"and":[84,100,127,147,174,265],"mainly":[85],"enhanced":[86,282],"targeted.":[92],"Hydrophobic":[93],"residues":[94,210],"preferred":[96],"208":[99],"213.":[101],"The":[102,202,251],"prodrug":[103],"today":[106],"primarily":[107],"used":[108],"for":[109,121,184,200,249],"maintaining":[110],"remission":[111],"inflammatory":[113],"bowel":[114],"disease.":[115],"Therapy":[116],"leads":[117],"adverse":[119,177,274],"effects":[120],"30":[122],"%":[123],"patients":[126],"genotyping":[128],"metabolic":[131],"genes":[132],"involved":[133],"can":[134],"explain":[135],"some":[136],"incidences.":[139],"Five":[140],"genotypes":[141],"characterized":[146],"variant":[148],"A2*E":[149,196,267],"had":[150,206],"3\u20134-fold":[151],"with":[155,223,280],"azathioprine,":[156],"due":[157],"proline":[160],"mutated":[161,213],"close":[162],"H-site.":[165],"Faster":[166],"activation":[167,260],"might":[168,293],"lead":[169],"different":[171],"metabolite":[172],"distributions":[173],"possibly":[175,271],"more":[176],"effects.":[178],"Genotyping":[179],"recommended":[183],"further":[185],"studies.":[186],"Molecular":[187],"docking":[188],"modeled":[193],"structure":[194,228],"suggested":[197],"three":[198],"mutagenesis.":[201],"mutants":[205],"small":[207],"or":[208],"polar":[209],"positions.":[214],"Mutant":[215],"L107G/L108D/F222H":[216],"displayed":[217],"70-fold":[219],"improved":[220],"azathioprine.":[224],"Determination":[225],"its":[227],"by":[229],"X-ray":[230],"crystallography":[231],"showed":[232],"widened":[234],"H-site,":[235],"suggesting":[236],"transition":[239],"state":[240],"could":[241],"be":[242],"accommodated":[243],"mode":[246],"better":[247],"suited":[248],"catalysis.":[250],"mutational":[252],"increased":[254],"our":[255],"understanding":[256],"highlighted":[266],"one":[269],"factor":[270],"behind":[272],"drug-effects.":[275],"A":[276],"successfully":[277],"redesigned":[278],"GST,":[279],"200-fold":[281],"towards":[285],"starting":[290],"point":[291],"A2*C,":[292],"find":[294],"use":[295],"enzyme-prodrug":[298],"therapies.":[299]},"counts_by_year":[{"year":2014,"cited_by_count":1}],"updated_date":"2026-11-06T12:05:46.655746","created_date":"2016-06-24T00:00:00"}
