{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,1,13]],"date-time":"2026-01-13T07:13:23Z","timestamp":1768288403428,"version":"3.49.0"},"reference-count":71,"publisher":"Wiley","issue":"38","license":[{"start":{"date-parts":[[2017,6,14]],"date-time":"2017-06-14T00:00:00Z","timestamp":1497398400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/501100007601","name":"Horizon 2020","doi-asserted-by":"publisher","award":["POCI\/01\/0145\/FEDER\/007728"],"award-info":[{"award-number":["POCI\/01\/0145\/FEDER\/007728"]}],"id":[{"id":"10.13039\/501100007601","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001871","name":"Funda\u00e7\u00e3o para a Ci\u00eancia e a Tecnologia","doi-asserted-by":"publisher","award":["PT2020 UID\/MULTI\/04378\/2013.UID\/MULTI\/04378\/2013"],"award-info":[{"award-number":["PT2020 UID\/MULTI\/04378\/2013.UID\/MULTI\/04378\/2013"]}],"id":[{"id":"10.13039\/501100001871","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001871","name":"Funda\u00e7\u00e3o para a Ci\u00eancia e a Tecnologia","doi-asserted-by":"publisher","award":["IF\/01310\/2013"],"award-info":[{"award-number":["IF\/01310\/2013"]}],"id":[{"id":"10.13039\/501100001871","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001871","name":"Funda\u00e7\u00e3o para a Ci\u00eancia e a Tecnologia","doi-asserted-by":"publisher","award":["EXCL-II\/QEQ-COM\/0394\/2012"],"award-info":[{"award-number":["EXCL-II\/QEQ-COM\/0394\/2012"]}],"id":[{"id":"10.13039\/501100001871","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100010662","name":"H2020 Excellent Science","doi-asserted-by":"publisher","award":["NORTE-01-0145-FEDER-000024"],"award-info":[{"award-number":["NORTE-01-0145-FEDER-000024"]}],"id":[{"id":"10.13039\/100010662","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Chemistry A European J"],"published-print":{"date-parts":[[2017,7,6]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>The catalytic mechanism of histidine decarboxylase (HDC), a pyridoxal\u20105\u2032\u2010phosphate (PLP)\u2010dependent enzyme, was studied by using a computational QM\/MM approach following the scheme M06\u20102X\/6\u2013311++G(3df,2pd):Amber. The reaction involves two sequential steps: the decarboxylation of <jats:sc>l<\/jats:sc>\u2010histidine and the protonation of the generated intermediate from which results histamine. The rate\u2010limiting step is the first one (\u0394<jats:italic>G<\/jats:italic><jats:sup>\u2260<\/jats:sup>=17.6\u2005kcal\u2009mol<jats:sup>\u22121<\/jats:sup>; \u0394<jats:italic>G<\/jats:italic><jats:sub>r<\/jats:sub>=13.7\u2005kcal\u2009mol<jats:sup>\u22121<\/jats:sup>) and agrees closely with the available experimental <jats:italic>k<\/jats:italic><jats:sub>cat<\/jats:sub> (1.73\u2005s<jats:sup>\u22121<\/jats:sup>), which corresponds to an activation barrier of 17.9\u2005kcal\u2009mol<jats:sup>\u22121<\/jats:sup>. In contrast, the second step is very fast (\u0394<jats:italic>G<\/jats:italic><jats:sup>\u2260<\/jats:sup>=1.9\u2005kcal\u2009mol<jats:sup>\u22121<\/jats:sup>) and exergonic (\u0394<jats:italic>G<\/jats:italic><jats:sub>r<\/jats:sub>=\u221233.2\u2005kcal\u2009mol<jats:sup>\u22121<\/jats:sup>). Our results agree with the available experimental data and allow us to explain the role played by several active site residues that are considered relevant according to site\u2010directed mutagenesis studies, namely Tyr334B, Asp273A, Lys305A, and Ser354B. These results can provide insights regarding the catalytic mechanism of other enzymes belonging to family II of PLP\u2010dependent decarboxylases.<\/jats:p>","DOI":"10.1002\/chem.201701375","type":"journal-article","created":{"date-parts":[[2017,6,14]],"date-time":"2017-06-14T07:42:41Z","timestamp":1497426161000},"page":"9162-9173","source":"Crossref","is-referenced-by-count":33,"title":["The Catalytic Mechanism of the Pyridoxal\u20105\u2032\u2010phosphate\u2010Dependent Enzyme, Histidine Decarboxylase: A Computational Study"],"prefix":"10.1002","volume":"23","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-9280-1838","authenticated-orcid":false,"given":"Henrique Silva","family":"Fernandes","sequence":"first","affiliation":[{"name":"UCIBIO-REQUIMTE Departamento de Qu\u00edmica e Bioqu\u00edmica Faculdade de Ci\u00eancias s\/n Universidade do Porto  4169-007 Porto Portugal"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7554-8324","authenticated-orcid":false,"given":"Maria Jo\u00e3o","family":"Ramos","sequence":"additional","affiliation":[{"name":"UCIBIO-REQUIMTE Departamento de Qu\u00edmica e Bioqu\u00edmica Faculdade de Ci\u00eancias s\/n Universidade do Porto  4169-007 Porto Portugal"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0342-7424","authenticated-orcid":false,"given":"Nuno M. F. S. A.","family":"Cerqueira","sequence":"additional","affiliation":[{"name":"UCIBIO-REQUIMTE Departamento de Qu\u00edmica e Bioqu\u00edmica Faculdade de Ci\u00eancias s\/n Universidade do Porto  4169-007 Porto Portugal"}]}],"member":"311","published-online":{"date-parts":[[2017,6,14]]},"reference":[{"key":"e_1_2_7_1_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbrc.2014.08.022"},{"key":"e_1_2_7_2_1","doi-asserted-by":"publisher","DOI":"10.1248\/bpb.35.91"},{"key":"e_1_2_7_3_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jdermsci.2012.05.010"},{"key":"e_1_2_7_4_1","doi-asserted-by":"publisher","DOI":"10.1002\/eji.201343838"},{"key":"e_1_2_7_5_1","doi-asserted-by":"publisher","DOI":"10.1111\/bjd.13199"},{"key":"e_1_2_7_6_1","doi-asserted-by":"publisher","DOI":"10.1111\/exd.12644"},{"key":"e_1_2_7_7_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1398-9995.2010.02425.x"},{"key":"e_1_2_7_8_1","unstructured":"\u00a0"},{"key":"e_1_2_7_9_2","doi-asserted-by":"crossref","first-page":"562","DOI":"10.1016\/S0016-5085(66)80034-3","volume":"50","author":"Guth P. H.","year":"1966","journal-title":"Gastroenterology"},{"key":"e_1_2_7_10_2","doi-asserted-by":"publisher","DOI":"10.1007\/BF01966762"},{"key":"e_1_2_7_11_1","first-page":"965056","volume":"2015","author":"Alkan M.","year":"2015","journal-title":"Exp. Diabetes Res."},{"key":"e_1_2_7_12_1","doi-asserted-by":"publisher","DOI":"10.1172\/JCI25713"},{"key":"e_1_2_7_13_1","unstructured":"\u00a0"},{"key":"e_1_2_7_14_2","doi-asserted-by":"publisher","DOI":"10.1097\/01.MP.0000044485.14910.3A"},{"key":"e_1_2_7_15_2","doi-asserted-by":"publisher","DOI":"10.1097\/00008390-200306000-00003"},{"key":"e_1_2_7_16_2","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0097728"},{"key":"e_1_2_7_17_2","doi-asserted-by":"publisher","DOI":"10.1007\/s000110300062"},{"key":"e_1_2_7_18_2","doi-asserted-by":"publisher","DOI":"10.1111\/j.1440-1827.2004.01641.x"},{"key":"e_1_2_7_19_2","doi-asserted-by":"publisher","DOI":"10.1007\/s12253-012-9584-y"},{"key":"e_1_2_7_20_1","unstructured":"\u00a0"},{"key":"e_1_2_7_21_2","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M112.381897"},{"key":"e_1_2_7_22_2","doi-asserted-by":"publisher","DOI":"10.1096\/fj.12-223867"},{"key":"e_1_2_7_23_2","doi-asserted-by":"publisher","DOI":"10.1007\/BF01993112"},{"key":"e_1_2_7_24_1","unstructured":"\u00a0"},{"key":"e_1_2_7_25_2","doi-asserted-by":"publisher","DOI":"10.1002\/bies.20174"},{"key":"e_1_2_7_26_2","doi-asserted-by":"publisher","DOI":"10.1042\/bj3200365"},{"key":"e_1_2_7_27_1","doi-asserted-by":"publisher","DOI":"10.1038\/sj.embor.embor914"},{"key":"e_1_2_7_28_1","doi-asserted-by":"publisher","DOI":"10.1093\/oxfordjournals.jbchem.a003240"},{"key":"e_1_2_7_29_1","unstructured":"\u00a0"},{"key":"e_1_2_7_30_2","doi-asserted-by":"publisher","DOI":"10.1021\/ct1002219"},{"key":"e_1_2_7_31_2","doi-asserted-by":"publisher","DOI":"10.1021\/ja204229m"},{"key":"e_1_2_7_32_1","unstructured":"\u00a0"},{"key":"e_1_2_7_33_2","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M707434200"},{"key":"e_1_2_7_34_2","doi-asserted-by":"publisher","DOI":"10.1046\/j.1432-1033.2003.03834.x"},{"key":"e_1_2_7_35_1","doi-asserted-by":"publisher","DOI":"10.1016\/0006-291X(85)91894-7"},{"key":"e_1_2_7_36_1","doi-asserted-by":"publisher","DOI":"10.1042\/bj20031525"},{"key":"e_1_2_7_37_1","doi-asserted-by":"publisher","DOI":"10.1016\/0006-291X(87)90545-6"},{"key":"e_1_2_7_38_1","doi-asserted-by":"publisher","DOI":"10.1107\/S1744309112015692"},{"key":"e_1_2_7_39_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0223-5234(00)90170-3"},{"key":"e_1_2_7_40_1","unstructured":"D.\u2005A. Case T.\u2005A. Darden T.\u2005E. Cheatham C.\u2005L. Simmerling J. Wang R.\u2005E. Duke R. Luo R.\u2005C. Walker W. Zhang K.\u2005M. Merz B. Roberts S. Hayik A. Roitberg G. Seabra J. Swails A.\u2005W. Goetz I. Kolossv\u00e1ry K.\u2005F. Wong F. Paesani J. Vanicek R.\u2005M. Wolf J. Liu X. Wu S.\u2005R. Brozell T. Steinbrecher H. Gohlke Q. Cai X. Ye J. Wang M.\u2005J. Hsieh G. Cui D.\u2005R. Roe D.\u2005H. Mathews M.\u2005G. Seetin R. Salomon-Ferrer C. Sagui V. Babin T. Luchko S. Gusarov A. Kovalenko P.\u2005A. Kollman AMBER 12 University of California San Francisco 2012."},{"key":"e_1_2_7_41_1","unstructured":"\u00a0"},{"key":"e_1_2_7_42_2","doi-asserted-by":"publisher","DOI":"10.1021\/ct200133y"},{"key":"e_1_2_7_43_2","doi-asserted-by":"publisher","DOI":"10.1021\/ct100578z"},{"key":"e_1_2_7_44_1","doi-asserted-by":"publisher","DOI":"10.1002\/jcc.20035"},{"key":"e_1_2_7_45_1","doi-asserted-by":"publisher","DOI":"10.1002\/prot.21123"},{"key":"e_1_2_7_46_1","doi-asserted-by":"publisher","DOI":"10.1063\/1.2464095"},{"key":"e_1_2_7_47_1","unstructured":"\u00a0"},{"key":"e_1_2_7_48_2","doi-asserted-by":"publisher","DOI":"10.1002\/jcc.540160911"},{"key":"e_1_2_7_49_2","doi-asserted-by":"publisher","DOI":"10.1021\/jp962071j"},{"key":"e_1_2_7_50_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0166-1280(98)00475-8"},{"key":"e_1_2_7_51_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cplett.2004.06.011"},{"key":"e_1_2_7_52_1","unstructured":"\u00a0"},{"key":"e_1_2_7_53_2","doi-asserted-by":"publisher","DOI":"10.1021\/acs.accounts.5b00333"},{"key":"e_1_2_7_54_2","doi-asserted-by":"publisher","DOI":"10.1021\/ja310165u"},{"key":"e_1_2_7_55_2","doi-asserted-by":"publisher","DOI":"10.1002\/chem.201600305"},{"key":"e_1_2_7_56_2","doi-asserted-by":"publisher","DOI":"10.1021\/acscatal.5b01928"},{"key":"e_1_2_7_57_2","doi-asserted-by":"publisher","DOI":"10.1039\/C6CY00356G"},{"key":"e_1_2_7_58_2","doi-asserted-by":"publisher","DOI":"10.1021\/acscatal.5b00759"},{"key":"e_1_2_7_59_1","unstructured":"Gaussian\u200909 Revision D.01 M.\u2005J. Frisch G.\u2005W. Trucks H.\u2005B. Schlegel G.\u2005E. Scuseria M.\u2005A. Robb J.\u2005R. Cheeseman G. Scalmani V. Barone B. Mennucci G.\u2005A. Petersson H. Nakatsuji M. Caricato X. Li H.\u2005P. Hratchian A.\u2005F. Izmaylov J. Bloino G. Zheng J.\u2005L. Sonnenberg M. Hada M. Ehara K. Toyota R. Fukuda J. Hasegawa M. Ishida T. Nakajima Y. Honda O. Kitao H. Nakai T. Vreven J.\u2005A. Montgomery \u2005Jr. J.\u2005E. Peralta F. Ogliaro M.\u2005J. Bearpark J. Heyd E.\u2005N. Brothers K.\u2005N. Kudin V.\u2005N. Staroverov R. Kobayashi J. Normand K. Raghavachari A.\u2005P. Rendell J.\u2005C. Burant S.\u2005S. Iyengar J. Tomasi M. Cossi N. Rega N.\u2005J. Millam M. Klene J.\u2005E. Knox J.\u2005B. Cross V. Bakken C. Adamo J. Jaramillo R. Gomperts R.\u2005E. Stratmann O. Yazyev A.\u2005J. Austin R. Cammi C. Pomelli J.\u2005W. Ochterski R.\u2005L. Martin K. Morokuma V.\u2005G. Zakrzewski G.\u2005A. Voth P. Salvador J.\u2005J. Dannenberg S. Dapprich A.\u2005D. Daniels \u00d6. Farkas J.\u2005B. Foresman J.\u2005V. Ortiz J. Cioslowski D.\u2005J. Fox Gaussian Inc. Wallingford CT 2009."},{"key":"e_1_2_7_60_1","doi-asserted-by":"publisher","DOI":"10.1021\/ar00072a001"},{"key":"e_1_2_7_61_1","unstructured":"J.\u2005W. Ochterski Thermochemistry in Gaussian 2000 p.\u200919."},{"key":"e_1_2_7_62_1","unstructured":"\u00a0"},{"key":"e_1_2_7_63_2","doi-asserted-by":"publisher","DOI":"10.1063\/1.3382344"},{"key":"e_1_2_7_64_2","doi-asserted-by":"publisher","DOI":"10.1002\/jcc.21759"},{"key":"e_1_2_7_65_1","doi-asserted-by":"publisher","DOI":"10.1002\/jcc.540050204"},{"key":"e_1_2_7_66_1","doi-asserted-by":"publisher","DOI":"10.1016\/0263-7855(96)00018-5"},{"key":"e_1_2_7_67_1","unstructured":"T.\u2005K. Roy\u2005Dennington John Millam 5.0.8 ed. Semichem Inc. Shawnee Mission 2009."},{"key":"e_1_2_7_68_1","doi-asserted-by":"publisher","DOI":"10.1021\/bi00054a011"},{"key":"e_1_2_7_69_1","unstructured":"\u00a0"},{"key":"e_1_2_7_70_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.55.4.712"},{"key":"e_1_2_7_71_2","doi-asserted-by":"publisher","DOI":"10.1002\/9780470122808.ch3"}],"container-title":["Chemistry \u2013 A European Journal"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.wiley.com\/onlinelibrary\/tdm\/v1\/articles\/10.1002%2Fchem.201701375","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/chemistry-europe.onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/chem.201701375","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,12]],"date-time":"2025-10-12T10:32:47Z","timestamp":1760265167000},"score":1,"resource":{"primary":{"URL":"https:\/\/chemistry-europe.onlinelibrary.wiley.com\/doi\/10.1002\/chem.201701375"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2017,6,14]]},"references-count":71,"journal-issue":{"issue":"38","published-print":{"date-parts":[[2017,7,6]]}},"alternative-id":["10.1002\/chem.201701375"],"URL":"https:\/\/doi.org\/10.1002\/chem.201701375","archive":["Portico"],"relation":{},"ISSN":["0947-6539","1521-3765"],"issn-type":[{"value":"0947-6539","type":"print"},{"value":"1521-3765","type":"electronic"}],"subject":[],"published":{"date-parts":[[2017,6,14]]}}}