{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,10,13]],"date-time":"2025-10-13T00:52:43Z","timestamp":1760316763678,"version":"build-2065373602"},"reference-count":113,"publisher":"Wiley","issue":"18","license":[{"start":{"date-parts":[[2021,7,16]],"date-time":"2021-07-16T00:00:00Z","timestamp":1626393600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"content-domain":{"domain":["chemistry-europe.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["ChemMedChem"],"published-print":{"date-parts":[[2021,9,16]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Since its discovery at the beginning of the past century, the essential nutrient <jats:sc>l<\/jats:sc>\u2010Tryptophan (<jats:sc>l<\/jats:sc>\u2010Trp) and its catabolic pathways have acquired an increasing interest in an ever wider scientific community for their pivotal roles in underlying many important physiological functions and associated pathological conditions. As a consequence, enzymes catalyzing rate limiting steps along <jats:sc>l<\/jats:sc>\u2010Trp catabolic pathways \u2010 including IDO1, TDO, TPH1 and TPH2 \u2010 have turned to be interesting drug targets for the design and development of novel therapeutic agents for different disorders such as carcinoid syndrome, cancer and autoimmune diseases. This article provides a fresh comparative overview on the most recent advancements that crystallographic studies, biophysical and computational works have brought on structural aspects and molecular recognition patterns of these enzymes toward <jats:sc>l<\/jats:sc>\u2010Trp. Finally, a conformational analysis of <jats:sc>l<\/jats:sc>\u2010Trp is also discussed as part of the molecular recognition process governing the binding of a substrate to its cognate enzymes.<\/jats:p>","DOI":"10.1002\/cmdc.202100312","type":"journal-article","created":{"date-parts":[[2021,6,17]],"date-time":"2021-06-17T04:58:26Z","timestamp":1623905906000},"page":"2732-2743","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["One Key and Multiple Locks: Substrate Binding in Structures of Tryptophan Dioxygenases and Hydroxylases"],"prefix":"10.1002","volume":"16","author":[{"given":"Andrea","family":"Mammoli","sequence":"first","affiliation":[{"name":"Department of Pharmaceutical Sciences University of Perugia  Via del Liceo N.\u20051 06123 Perugia Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Alessandra","family":"Riccio","sequence":"additional","affiliation":[{"name":"Department of Pharmaceutical Sciences University of Perugia  Via del Liceo N.\u20051 06123 Perugia Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Elisa","family":"Bianconi","sequence":"additional","affiliation":[{"name":"Department of Pharmaceutical Sciences University of Perugia  Via del Liceo N.\u20051 06123 Perugia Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Alice","family":"Coletti","sequence":"additional","affiliation":[{"name":"Department of Medicine and Surgery University of Perugia  P. le Gambuli 06132 Perugia Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Emidio","family":"Camaioni","sequence":"additional","affiliation":[{"name":"Department of Pharmaceutical Sciences University of Perugia  Via del Liceo N.\u20051 06123 Perugia Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9535-4183","authenticated-orcid":false,"given":"Antonio","family":"Macchiarulo","sequence":"additional","affiliation":[{"name":"Department of Pharmaceutical Sciences University of Perugia  Via del Liceo N.\u20051 06123 Perugia Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2021,7,16]]},"reference":[{"key":"e_1_2_9_1_1","doi-asserted-by":"publisher","DOI":"10.1113\/jphysiol.1901.sp000880"},{"key":"e_1_2_9_2_1","doi-asserted-by":"publisher","DOI":"10.1016\/bs.acc.2019.08.005"},{"key":"e_1_2_9_3_1","first-page":"13","volume":"44","author":"Palmer S.","year":"1990","journal-title":"Eur. J. Clin. Nutr."},{"key":"e_1_2_9_4_1","doi-asserted-by":"publisher","DOI":"10.1017\/S0029665199000348"},{"key":"e_1_2_9_5_1","doi-asserted-by":"publisher","DOI":"10.1079\/BJN19830068"},{"key":"e_1_2_9_6_1","first-page":"1","author":"Frazer A.","year":"1999","journal-title":"Basic Neurochem."},{"key":"e_1_2_9_7_1","doi-asserted-by":"publisher","DOI":"10.1146\/annurev.med.60.042307.110802"},{"key":"e_1_2_9_8_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1471-4159.2004.02850.x"},{"key":"e_1_2_9_9_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.2233056100"},{"key":"e_1_2_9_10_1","doi-asserted-by":"publisher","DOI":"10.1021\/cn300154j"},{"key":"e_1_2_9_11_1","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.6684-10.2011"},{"key":"e_1_2_9_12_1","doi-asserted-by":"publisher","DOI":"10.1113\/jphysiol.2008.160416"},{"key":"e_1_2_9_13_1","doi-asserted-by":"publisher","DOI":"10.1080\/14728222.2017.1272581"},{"key":"e_1_2_9_14_1","doi-asserted-by":"publisher","DOI":"10.2174\/1875397301004010019"},{"key":"e_1_2_9_15_1","doi-asserted-by":"publisher","DOI":"10.1007\/s40265-017-0737-x"},{"key":"e_1_2_9_16_1","doi-asserted-by":"publisher","DOI":"10.1177\/1178646917691938"},{"key":"e_1_2_9_17_1","doi-asserted-by":"publisher","DOI":"10.4137\/IJTR.S2097"},{"key":"e_1_2_9_18_1","doi-asserted-by":"publisher","DOI":"10.1038\/nature13323"},{"key":"e_1_2_9_19_1","doi-asserted-by":"publisher","DOI":"10.1038\/nature10491"},{"key":"e_1_2_9_20_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1014465107"},{"key":"e_1_2_9_21_1","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.0903670"},{"key":"e_1_2_9_22_1","doi-asserted-by":"publisher","DOI":"10.1038\/nrd870"},{"key":"e_1_2_9_23_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuro.2012.11.007"},{"key":"e_1_2_9_24_1","doi-asserted-by":"publisher","DOI":"10.1021\/bi992997s"},{"key":"e_1_2_9_25_1","doi-asserted-by":"publisher","DOI":"10.4137\/IJTR.S2469"},{"key":"e_1_2_9_26_1","doi-asserted-by":"publisher","DOI":"10.1007\/978-1-4615-0135-0_6"},{"key":"e_1_2_9_27_1","doi-asserted-by":"publisher","DOI":"10.1021\/acs.jmedchem.5b00461"},{"key":"e_1_2_9_28_1","doi-asserted-by":"publisher","DOI":"10.1038\/nrd3793"},{"key":"e_1_2_9_29_1","doi-asserted-by":"publisher","DOI":"10.3390\/cells9061564"},{"key":"e_1_2_9_30_1","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2020.00388"},{"key":"e_1_2_9_31_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.neubiorev.2021.01.018"},{"key":"e_1_2_9_32_1","doi-asserted-by":"publisher","DOI":"10.1042\/BST0370408"},{"key":"e_1_2_9_33_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00726-008-0137-3"},{"key":"e_1_2_9_34_1","doi-asserted-by":"publisher","DOI":"10.1039\/C7MD00109F"},{"key":"e_1_2_9_35_1","doi-asserted-by":"publisher","DOI":"10.7150\/jca.31727"},{"key":"e_1_2_9_36_1","doi-asserted-by":"publisher","DOI":"10.1080\/13543776.2019.1556638"},{"key":"e_1_2_9_37_1","doi-asserted-by":"publisher","DOI":"10.1096\/fasebj.5.11.1907934"},{"key":"e_1_2_9_38_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0021-9258(19)86035-0"},{"key":"e_1_2_9_39_1","doi-asserted-by":"publisher","DOI":"10.1021\/cr9500500"},{"key":"e_1_2_9_40_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.biocel.2008.01.005"},{"key":"e_1_2_9_41_1","doi-asserted-by":"publisher","DOI":"10.1016\/S1471-4906(03)00072-3"},{"key":"e_1_2_9_42_1","doi-asserted-by":"publisher","DOI":"10.1038\/nri1457"},{"key":"e_1_2_9_43_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.gene.2007.04.010"},{"key":"e_1_2_9_44_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1918215117"},{"key":"e_1_2_9_45_1","doi-asserted-by":"publisher","DOI":"10.1038\/srep35169"},{"key":"e_1_2_9_46_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-017-01725-8"},{"key":"e_1_2_9_47_1","doi-asserted-by":"publisher","DOI":"10.1002\/cmdc.201900529"},{"key":"e_1_2_9_48_1","doi-asserted-by":"publisher","DOI":"10.1021\/bi702393b"},{"key":"e_1_2_9_49_1","doi-asserted-by":"publisher","DOI":"10.1021\/bi201439m"},{"key":"e_1_2_9_50_1","doi-asserted-by":"publisher","DOI":"10.1002\/prot.24653"},{"key":"e_1_2_9_51_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.0508996103"},{"key":"e_1_2_9_52_1","doi-asserted-by":"publisher","DOI":"10.1002\/cmdc.202000116"},{"key":"e_1_2_9_53_1","doi-asserted-by":"publisher","DOI":"10.1111\/jcmm.12954"},{"key":"e_1_2_9_54_1","doi-asserted-by":"publisher","DOI":"10.15252\/embr.201949756"},{"key":"e_1_2_9_55_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbapap.2007.06.007"},{"key":"e_1_2_9_56_1","doi-asserted-by":"publisher","DOI":"10.1002\/minf.201501038"},{"key":"e_1_2_9_57_1","doi-asserted-by":"publisher","DOI":"10.1021\/acs.biochem.6b00077"},{"key":"e_1_2_9_58_1","doi-asserted-by":"publisher","DOI":"10.1107\/S2059798320013510"},{"key":"e_1_2_9_59_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M109.039859"},{"key":"e_1_2_9_60_1","doi-asserted-by":"publisher","DOI":"10.1021\/ja9029768"},{"key":"e_1_2_9_61_1","doi-asserted-by":"publisher","DOI":"10.1021\/bi1005078"},{"key":"e_1_2_9_62_1","doi-asserted-by":"publisher","DOI":"10.1107\/S2053230X18012955"},{"key":"e_1_2_9_63_1","doi-asserted-by":"publisher","DOI":"10.1021\/ja208694g"},{"key":"e_1_2_9_64_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.abb.2015.02.014"},{"key":"e_1_2_9_65_1","doi-asserted-by":"publisher","DOI":"10.1021\/jacs.8b03691"},{"key":"e_1_2_9_66_1","doi-asserted-by":"publisher","DOI":"10.1021\/ci800414v"},{"key":"e_1_2_9_67_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jmgm.2007.04.010"},{"key":"e_1_2_9_68_1","doi-asserted-by":"publisher","DOI":"10.1021\/bi702405a"},{"key":"e_1_2_9_69_1","doi-asserted-by":"publisher","DOI":"10.1111\/febs.13834"},{"key":"e_1_2_9_70_1","doi-asserted-by":"publisher","DOI":"10.1002\/9780470122778.ch3"},{"key":"e_1_2_9_71_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0021-9258(19)63693-8"},{"key":"e_1_2_9_72_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M200457200"},{"key":"e_1_2_9_73_1","doi-asserted-by":"publisher","DOI":"10.1021\/bi101732n"},{"key":"e_1_2_9_74_1","doi-asserted-by":"publisher","DOI":"10.1021\/ja803107w"},{"key":"e_1_2_9_75_1","doi-asserted-by":"publisher","DOI":"10.1021\/ja808326g"},{"key":"e_1_2_9_76_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00775-010-0646-x"},{"key":"e_1_2_9_77_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.0906655106"},{"key":"e_1_2_9_78_1","doi-asserted-by":"publisher","DOI":"10.1021\/ja103530v"},{"key":"e_1_2_9_79_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M115.695684"},{"key":"e_1_2_9_80_1","doi-asserted-by":"publisher","DOI":"10.1021\/bi0513958"},{"key":"e_1_2_9_81_1","doi-asserted-by":"publisher","DOI":"10.1002\/prot.24653"},{"key":"e_1_2_9_82_1","doi-asserted-by":"publisher","DOI":"10.1002\/jez.b.22608"},{"key":"e_1_2_9_83_1","first-page":"55","author":"Basran J.","year":"2016","journal-title":"Biochemistry."},{"key":"e_1_2_9_84_1","doi-asserted-by":"publisher","DOI":"10.1042\/BST0361120"},{"key":"e_1_2_9_85_1","doi-asserted-by":"publisher","DOI":"10.1093\/jb\/mvp002"},{"key":"e_1_2_9_86_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ymgme.2017.02.009"},{"key":"e_1_2_9_87_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0021-9258(19)50967-X"},{"key":"e_1_2_9_88_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0021-9258(18)98149-4"},{"key":"e_1_2_9_89_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M111.253237"},{"key":"e_1_2_9_90_1","doi-asserted-by":"publisher","DOI":"10.1146\/annurev.biochem.68.1.355"},{"key":"e_1_2_9_91_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbrc.2016.05.144"},{"key":"e_1_2_9_92_1","doi-asserted-by":"publisher","DOI":"10.1002\/iub.1144"},{"key":"e_1_2_9_93_1","doi-asserted-by":"publisher","DOI":"10.1021\/bi026561f"},{"key":"e_1_2_9_94_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bmcl.2009.07.005"},{"key":"e_1_2_9_95_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bmcl.2016.04.057"},{"key":"e_1_2_9_96_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bmcl.2016.12.053"},{"key":"e_1_2_9_97_1","doi-asserted-by":"publisher","DOI":"10.1021\/bi8015263"},{"key":"e_1_2_9_98_1","doi-asserted-by":"publisher","DOI":"10.1006\/jmbi.2000.4097"},{"key":"e_1_2_9_99_1","doi-asserted-by":"publisher","DOI":"10.1021\/bi015722x"},{"key":"e_1_2_9_100_1","doi-asserted-by":"publisher","DOI":"10.1006\/bbrc.2002.6719"},{"key":"e_1_2_9_101_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1471-4159.2005.03604.x"},{"key":"e_1_2_9_102_1","doi-asserted-by":"publisher","DOI":"10.1126\/science.1097540"},{"key":"e_1_2_9_103_1","doi-asserted-by":"publisher","DOI":"10.1046\/j.1471-4159.1997.68052220.x"},{"key":"e_1_2_9_104_1","doi-asserted-by":"publisher","DOI":"10.1046\/j.1471-4159.1997.69041738.x"},{"key":"e_1_2_9_105_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1471-4159.2007.04855.x"},{"key":"e_1_2_9_106_1","doi-asserted-by":"publisher","DOI":"10.1042\/BJ20071033"},{"key":"e_1_2_9_107_1","doi-asserted-by":"publisher","DOI":"10.1038\/nbt999"},{"key":"e_1_2_9_108_1","doi-asserted-by":"publisher","DOI":"10.1021\/jm030563w"},{"key":"e_1_2_9_109_1","doi-asserted-by":"publisher","DOI":"10.1039\/C4MD00024B"},{"key":"e_1_2_9_110_1","doi-asserted-by":"publisher","DOI":"10.1021\/acs.jcim.9b00373"},{"key":"e_1_2_9_111_1","doi-asserted-by":"publisher","DOI":"10.1021\/ja076186k"},{"key":"e_1_2_9_112_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0021-9258(19)77982-4"},{"key":"e_1_2_9_113_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00726-014-1766-3"}],"container-title":["ChemMedChem"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/cmdc.202100312","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/full-xml\/10.1002\/cmdc.202100312","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/chemistry-europe.onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/cmdc.202100312","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,12]],"date-time":"2025-10-12T18:06:56Z","timestamp":1760292416000},"score":1,"resource":{"primary":{"URL":"https:\/\/chemistry-europe.onlinelibrary.wiley.com\/doi\/10.1002\/cmdc.202100312"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2021,7,16]]},"references-count":113,"journal-issue":{"issue":"18","published-print":{"date-parts":[[2021,9,16]]}},"alternative-id":["10.1002\/cmdc.202100312"],"URL":"https:\/\/doi.org\/10.1002\/cmdc.202100312","archive":["Portico"],"relation":{},"ISSN":["1860-7179","1860-7187"],"issn-type":[{"type":"print","value":"1860-7179"},{"type":"electronic","value":"1860-7187"}],"subject":[],"published":{"date-parts":[[2021,7,16]]},"assertion":[{"value":"2021-06-05","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2021-07-16","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}