{"id":"https://openalex.org/W15650018","doi":null,"title":"Structural insights into the mechanism and inhibition of prostaglandin H2 synthase-1","display_name":"Structural insights into the mechanism and inhibition of prostaglandin H2 synthase-1","publication_year":2003,"publication_date":"2003-01-01","ids":{"openalex":"https://openalex.org/W15650018","mag":"15650018"},"language":"en","primary_location":{"id":"pmh:oai:repository.upenn.edu:dissertations-3596","doi":null,"is_oa":false,"landing_page_url":"https://repository.upenn.edu/dissertations/AAI3095886","pdf_url":null,"source":{"id":"https://openalex.org/S4377196331","display_name":"Scholarly Commons (University of Pennsylvania)","issn_l":null,"issn":null,"is_oa":false,"is_in_doaj":false,"is_core":false,"listed_in":[],"host_organization":"https://openalex.org/I79576946","host_organization_name":"University of Pennsylvania","host_organization_lineage":["https://openalex.org/I79576946"],"host_organization_lineage_names":[],"type":"repository"},"license":null,"license_id":null,"version":"submittedVersion","is_accepted":false,"is_published":false,"raw_source_name":"Dissertations available from ProQuest","raw_type":"text"},"volume":null,"type":"dissertation","is_traditional":true,"indexed_in":[],"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/A5050299360","display_name":"Kushol Gupta","orcid":"https://orcid.org/0000-0002-7006-2667","observed_orcids":["https://orcid.org/0000-0002-7006-2667"]},"institutions":[],"countries":[],"is_corresponding":true,"raw_author_name":"Kushol Gupta","raw_affiliation_strings":[],"raw_orcid":"https://orcid.org/0000-0002-7006-2667","affiliations":[]}],"institutions":[],"countries_distinct_count":0,"institutions_distinct_count":0,"corresponding_author_ids":["https://openalex.org/A5050299360"],"corresponding_institution_ids":[],"apc_list":null,"apc_paid":null,"fwci":null,"has_fulltext":false,"cited_by_count":0,"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/T10678","display_name":"Inflammatory mediators and NSAID effects","score":0.6050000190734863,"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/T10678","display_name":"Inflammatory mediators and NSAID effects","score":0.6050000190734863,"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/T11162","display_name":"Enzyme Structure and Function","score":0.3176000118255615,"subfield":{"id":"https://openalex.org/subfields/1315","display_name":"Structural 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/T11747","display_name":"Metal-Catalyzed Oxygenation Mechanisms","score":0.03180000185966492,"subfield":{"id":"https://openalex.org/subfields/1604","display_name":"Inorganic Chemistry"},"field":{"id":"https://openalex.org/fields/16","display_name":"Chemistry"},"domain":{"id":"https://openalex.org/domains/3","display_name":"Physical Sciences"}}],"keywords":[{"id":"https://openalex.org/keywords/prostaglandin-h-synthase-1","display_name":"PGHS-1","score":0.7799999713897705},{"id":"https://openalex.org/keywords/prostaglandin-h-synthase-2","display_name":"prostaglandin H synthase-2","score":0.8939999938011169},{"id":"https://openalex.org/keywords/nonsteroidal-anti-inflammatory-drugs","display_name":"nonsteroidal anti-inflammatory drugs","score":0.8690000176429749},{"id":"https://openalex.org/keywords/arachidonic-acid-metabolism","display_name":"arachidonic acid metabolism","score":0.7860000133514404},{"id":"https://openalex.org/keywords/prostanoids","display_name":"prostanoids","score":0.8790000081062317},{"id":"https://openalex.org/keywords/enzyme-inhibition-mechanism","display_name":"enzyme inhibition mechanism","score":0.7039999961853027},{"id":"https://openalex.org/keywords/homodimer-structure","display_name":"homodimer structure","score":0.593999981880188}],"concepts":[{"id":"https://openalex.org/C89611455","wikidata":"https://www.wikidata.org/wiki/Q6804646","display_name":"Mechanism (biology)","level":2,"score":0.6583516597747803},{"id":"https://openalex.org/C112243037","wikidata":"https://www.wikidata.org/wiki/Q22327117","display_name":"ATP synthase","level":3,"score":0.5343559980392456},{"id":"https://openalex.org/C185592680","wikidata":"https://www.wikidata.org/wiki/Q2329","display_name":"Chemistry","level":0,"score":0.44016820192337036},{"id":"https://openalex.org/C2780978440","wikidata":"https://www.wikidata.org/wiki/Q416567","display_name":"Prostaglandin H2","level":4,"score":0.4286156892776489},{"id":"https://openalex.org/C2780664492","wikidata":"https://www.wikidata.org/wiki/Q209717","display_name":"Prostaglandin","level":2,"score":0.42516466975212097},{"id":"https://openalex.org/C55493867","wikidata":"https://www.wikidata.org/wiki/Q7094","display_name":"Biochemistry","level":1,"score":0.28829801082611084},{"id":"https://openalex.org/C181199279","wikidata":"https://www.wikidata.org/wiki/Q8047","display_name":"Enzyme","level":2,"score":0.2540099024772644},{"id":"https://openalex.org/C138885662","wikidata":"https://www.wikidata.org/wiki/Q5891","display_name":"Philosophy","level":0,"score":0.10730046033859253},{"id":"https://openalex.org/C111472728","wikidata":"https://www.wikidata.org/wiki/Q9471","display_name":"Epistemology","level":1,"score":0.10155779123306274},{"id":"https://openalex.org/C2778078955","wikidata":"https://www.wikidata.org/wiki/Q407699","display_name":"Arachidonic acid","level":3,"score":0.0}],"mesh":[],"locations_count":2,"locations":[{"id":"pmh:oai:repository.upenn.edu:dissertations-3596","doi":null,"is_oa":false,"landing_page_url":"https://repository.upenn.edu/dissertations/AAI3095886","pdf_url":null,"source":{"id":"https://openalex.org/S4377196331","display_name":"Scholarly Commons (University of Pennsylvania)","issn_l":null,"issn":null,"is_oa":false,"is_in_doaj":false,"is_core":false,"listed_in":[],"host_organization":"https://openalex.org/I79576946","host_organization_name":"University of Pennsylvania","host_organization_lineage":["https://openalex.org/I79576946"],"host_organization_lineage_names":[],"type":"repository"},"license":null,"license_id":null,"version":"submittedVersion","is_accepted":false,"is_published":false,"raw_source_name":"Dissertations available from ProQuest","raw_type":"text"},{"id":"mag:15650018","doi":null,"is_oa":false,"landing_page_url":"https://repository.upenn.edu/cgi/viewcontent.cgi?article=3596&context=dissertations","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":null,"sustainable_development_goals":[{"score":0.504800021648407,"display_name":"Good health and well-being","id":"https://metadata.un.org/sdg/3"}],"study_designs":[],"awards":[],"funders":[],"has_content":{"pdf":false,"grobid_xml":false},"content_urls":null,"referenced_works_count":242,"referenced_works":["https://openalex.org/W2024175","https://openalex.org/W124723856","https://openalex.org/W139520776","https://openalex.org/W140965324","https://openalex.org/W166881372","https://openalex.org/W203226604","https://openalex.org/W570080387","https://openalex.org/W1025607298","https://openalex.org/W1142815736","https://openalex.org/W1241551828","https://openalex.org/W1484510905","https://openalex.org/W1485442945","https://openalex.org/W1488753908","https://openalex.org/W1490609633","https://openalex.org/W1493409554","https://openalex.org/W1494920110","https://openalex.org/W1520750411","https://openalex.org/W1525772448","https://openalex.org/W1525841820","https://openalex.org/W1527453674","https://openalex.org/W1530087558","https://openalex.org/W1531513729","https://openalex.org/W1536157072","https://openalex.org/W1536572717","https://openalex.org/W1536681507","https://openalex.org/W1539796472","https://openalex.org/W1540429594","https://openalex.org/W1553503443","https://openalex.org/W1555602949","https://openalex.org/W1556997704","https://openalex.org/W1561747056","https://openalex.org/W1578742674","https://openalex.org/W1581184339","https://openalex.org/W1586433464","https://openalex.org/W1586663904","https://openalex.org/W1591927171","https://openalex.org/W1593186399","https://openalex.org/W1596000517","https://openalex.org/W1596621826","https://openalex.org/W1601641487","https://openalex.org/W1604764621","https://openalex.org/W1604766895","https://openalex.org/W1608437430","https://openalex.org/W1659584317","https://openalex.org/W1740416844","https://openalex.org/W1849012281","https://openalex.org/W1856590789","https://openalex.org/W1866116049","https://openalex.org/W1902547891","https://openalex.org/W1921815852","https://openalex.org/W1964088665","https://openalex.org/W1964237016","https://openalex.org/W1964665460","https://openalex.org/W1964695812","https://openalex.org/W1965782511","https://openalex.org/W1966183396","https://openalex.org/W1966340998","https://openalex.org/W1966828832","https://openalex.org/W1968162098","https://openalex.org/W1970287261","https://openalex.org/W1970934250","https://openalex.org/W1972563656","https://openalex.org/W1973122654","https://openalex.org/W1975262546","https://openalex.org/W1976422010","https://openalex.org/W1978721259","https://openalex.org/W1979107796","https://openalex.org/W1979131204","https://openalex.org/W1980530911","https://openalex.org/W1980742376","https://openalex.org/W1980881765","https://openalex.org/W1981974511","https://openalex.org/W1982083268","https://openalex.org/W1982943103","https://openalex.org/W1983131031","https://openalex.org/W1983203735","https://openalex.org/W1983749281","https://openalex.org/W1985785964","https://openalex.org/W1986191025","https://openalex.org/W1986369217","https://openalex.org/W1987212025","https://openalex.org/W1987731954","https://openalex.org/W1988056643","https://openalex.org/W1988578458","https://openalex.org/W1991987072","https://openalex.org/W1992041168","https://openalex.org/W1992102726","https://openalex.org/W1993267975","https://openalex.org/W1993325600","https://openalex.org/W1997761684","https://openalex.org/W1998049068","https://openalex.org/W1998846905","https://openalex.org/W1999156369","https://openalex.org/W1999590520","https://openalex.org/W1999678903","https://openalex.org/W2000724113","https://openalex.org/W2001163038","https://openalex.org/W2001223686","https://openalex.org/W2001641653","https://openalex.org/W2001978048","https://openalex.org/W2002033353","https://openalex.org/W2003092651","https://openalex.org/W2003684583","https://openalex.org/W2003897562","https://openalex.org/W2005861756","https://openalex.org/W2007187686","https://openalex.org/W2007408386","https://openalex.org/W2007504470","https://openalex.org/W2007796985","https://openalex.org/W2008424322","https://openalex.org/W2008469839","https://openalex.org/W2008574207","https://openalex.org/W2008708467","https://openalex.org/W2008994073","https://openalex.org/W2009768224","https://openalex.org/W2010311152","https://openalex.org/W2010967782","https://openalex.org/W2012447142","https://openalex.org/W2012684695","https://openalex.org/W2013064733","https://openalex.org/W2013083986","https://openalex.org/W2013769810","https://openalex.org/W2013910882","https://openalex.org/W2014416110","https://openalex.org/W2014503546","https://openalex.org/W2014845948","https://openalex.org/W2015448435","https://openalex.org/W2018314534","https://openalex.org/W2020429677","https://openalex.org/W2021687937","https://openalex.org/W2021737033","https://openalex.org/W2021745376","https://openalex.org/W2022040665","https://openalex.org/W2023200971","https://openalex.org/W2023302278","https://openalex.org/W2023603090","https://openalex.org/W2024289681","https://openalex.org/W2024715019","https://openalex.org/W2024998432","https://openalex.org/W2027991357","https://openalex.org/W2028231353","https://openalex.org/W2030109883","https://openalex.org/W2030505928","https://openalex.org/W2030850720","https://openalex.org/W2030940918","https://openalex.org/W2031772330","https://openalex.org/W2036651008","https://openalex.org/W2039358393","https://openalex.org/W2039562073","https://openalex.org/W2041160033","https://openalex.org/W2041309279","https://openalex.org/W2041498818","https://openalex.org/W2041879090","https://openalex.org/W2042017985","https://openalex.org/W2044844250","https://openalex.org/W2045097567","https://openalex.org/W2045373074","https://openalex.org/W2047012753","https://openalex.org/W2048234380","https://openalex.org/W2049771771","https://openalex.org/W2053797921","https://openalex.org/W2054535723","https://openalex.org/W2054556495","https://openalex.org/W2056782934","https://openalex.org/W2057534385","https://openalex.org/W2058291350","https://openalex.org/W2058638082","https://openalex.org/W2059750485","https://openalex.org/W2060425366","https://openalex.org/W2060994798","https://openalex.org/W2061062300","https://openalex.org/W2061592031","https://openalex.org/W2062641944","https://openalex.org/W2063144963","https://openalex.org/W2064498341","https://openalex.org/W2066074947","https://openalex.org/W2066395665","https://openalex.org/W2067227502","https://openalex.org/W2068104911","https://openalex.org/W2069059409","https://openalex.org/W2069772469","https://openalex.org/W2069812802","https://openalex.org/W2070386995","https://openalex.org/W2070671643","https://openalex.org/W2070770133","https://openalex.org/W2070797882","https://openalex.org/W2071338491","https://openalex.org/W2072688910","https://openalex.org/W2074668577","https://openalex.org/W2075316900","https://openalex.org/W2076833946","https://openalex.org/W2078179845","https://openalex.org/W2078340328","https://openalex.org/W2078715730","https://openalex.org/W2079406594","https://openalex.org/W2082615272","https://openalex.org/W2083805043","https://openalex.org/W2085680573","https://openalex.org/W2086458197","https://openalex.org/W2086514081","https://openalex.org/W2086847055","https://openalex.org/W2088621428","https://openalex.org/W2089619245","https://openalex.org/W2090359132","https://openalex.org/W2090431078","https://openalex.org/W2091502389","https://openalex.org/W2093065617","https://openalex.org/W2093683433","https://openalex.org/W2093758951","https://openalex.org/W2094761607","https://openalex.org/W2100417337","https://openalex.org/W2106882534","https://openalex.org/W2113745276","https://openalex.org/W2115350007","https://openalex.org/W2116947993","https://openalex.org/W2118728538","https://openalex.org/W2125240995","https://openalex.org/W2125289895","https://openalex.org/W2126853519","https://openalex.org/W2134266820","https://openalex.org/W2134873867","https://openalex.org/W2138393107","https://openalex.org/W2148152028","https://openalex.org/W2149083834","https://openalex.org/W2157204944","https://openalex.org/W2161475887","https://openalex.org/W2162355721","https://openalex.org/W2165885543","https://openalex.org/W2165898505","https://openalex.org/W2166827931","https://openalex.org/W2167590372","https://openalex.org/W2238132545","https://openalex.org/W2305823921","https://openalex.org/W2309355013","https://openalex.org/W2335803611","https://openalex.org/W2401692015","https://openalex.org/W2408889994","https://openalex.org/W2412086632","https://openalex.org/W2437033631","https://openalex.org/W2500515524","https://openalex.org/W2894728782","https://openalex.org/W2952210817"],"related_works":["https://openalex.org/W120813674","https://openalex.org/W4214595219","https://openalex.org/W22807086","https://openalex.org/W2081822067","https://openalex.org/W6987438164","https://openalex.org/W1565873079","https://openalex.org/W59889026","https://openalex.org/W2126853519","https://openalex.org/W1979107796","https://openalex.org/W1992041168"],"abstract_inverted_index":{"Prostanoids":[0],"are":[1,6,71,107],"fatty":[2],"acid":[3,62],"autocoids":[4],"that":[5],"involved":[7,91],"in":[8,57,81,92,100,223],"platelet":[9],"aggregation,":[10],"inflammation,":[11],"and":[12,48,165,202,228],"the":[13,65,68,112,126,142,146,156,166,192,209,212,218,224,229],"pathophysiology":[14],"of":[15,75,114,132,145,148,159,169,177,185,198,211,216,220,232],"cardiovascular":[16],"disease.":[17],"Prostaglandin":[18],"H2":[19],"synthase":[20],"(PGHS;":[21],"EC":[22],"1.14.99.1)":[23],"is":[24,86,98],"an":[25],"important":[26],"drug":[27],"target":[28],"essential":[29],"to":[30,59,67,102,109,136,140],"their":[31,82],"formation.":[32],"This":[33],"bifunctional":[34],"heme-dependent":[35],"enzyme":[36],"functions":[37],"as":[38,117],"a":[39,46,49,87,175],"homodimer,":[40],"where":[41],"each":[42],"monomer":[43],"contains":[44],"both":[45],"cyclooxygenase":[47,127,225],"peroxidase":[50,160],"active":[51,54,128,214,226],"site.":[52,129],"These":[53],"sites":[55,215],"work":[56],"concert":[58],"transform":[60],"arachidonic":[61],"into":[63,208],"PGH2,":[64],"precursor":[66],"prostanoids.":[69],"There":[70],"two":[72,213],"known":[73,116],"isoforms":[74,106],"this":[76,133,178],"enzyme,":[77],"which":[78,122],"differ":[79],"mainly":[80],"expression":[83,97],"patterns:":[84],"PGHS-1":[85,199],"constitutively":[88],"expressed":[89],"isoform":[90],"\u201chousekeeping\u201d":[93],"functions,":[94],"while":[95],"PGHS-2":[96],"induced":[99],"response":[101],"inflammatory":[103],"stimuli.":[104],"Both":[105],"susceptible":[108],"inhibition":[110],"by":[111,124,162],"class":[113],"drugs":[115,120],"nonsteroidal":[118],"antiinflammatory":[119],"(NSAIDs),":[121],"act":[123],"blocking":[125],"The":[130],"goal":[131],"dissertation":[134],"was":[135],"use":[137],"x-ray":[138,182],"crystallography":[139],"expand":[141],"current":[143],"understanding":[144],"structure":[147],"PGHS.":[149],"In":[150],"doing":[151],"so,":[152],"key":[153],"issues,":[154],"including":[155],"structural":[157,167,230],"consequences":[158,231],"impairment":[161],"protoporphyrin":[163,233],"substitution":[164],"basis":[168],"NSAID":[170],"binding":[171,222],"were":[172,187,200],"investigated.":[173],"As":[174],"result":[176],"study,":[179],"six":[180],"unique":[181],"crystal":[183],"structures":[184,197,205],"PGHS":[186],"determined.":[188],"Among":[189],"these":[190,204],"structures,":[191],"first":[193],"high-resolution":[194],"(2.0":[195],"\u00c5)":[196],"solved,":[201],"together":[203],"yield":[206],"insights":[207],"architecture":[210],"PGHS,":[217],"nature":[219],"inhibitor":[221],"site,":[227],"substitution.":[234]},"counts_by_year":[],"updated_date":"2026-11-04T10:54:05.112534","created_date":"2016-06-24T00:00:00"}