{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,14]],"date-time":"2026-04-14T18:03:53Z","timestamp":1776189833644,"version":"3.50.1"},"reference-count":75,"publisher":"Wiley","issue":"42","license":[{"start":{"date-parts":[[2015,8,21]],"date-time":"2015-08-21T00:00:00Z","timestamp":1440115200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/501100004895","name":"European Social Fund","doi-asserted-by":"crossref","award":["JaePre\u20022011\u200201248"],"award-info":[{"award-number":["JaePre\u20022011\u200201248"]}],"id":[{"id":"10.13039\/501100004895","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/501100004895","name":"European Social Fund","doi-asserted-by":"crossref","award":["AP2009-4092"],"award-info":[{"award-number":["AP2009-4092"]}],"id":[{"id":"10.13039\/501100004895","id-type":"DOI","asserted-by":"crossref"}]},{"name":"Andalusian Government","award":["CVI-BIO198"],"award-info":[{"award-number":["CVI-BIO198"]}]},{"DOI":"10.13039\/501100003329","name":"Ministry of Economy and Competitiveness","doi-asserted-by":"crossref","award":["BFU2012-31670"],"award-info":[{"award-number":["BFU2012-31670"]}],"id":[{"id":"10.13039\/501100003329","id-type":"DOI","asserted-by":"crossref"}]},{"name":"Ramon Areces Foundation"},{"name":"European Bio-NMR Project","award":["BIO-NMR-00130"],"award-info":[{"award-number":["BIO-NMR-00130"]}]},{"name":"Centro de Investigaci\u00f3n Tecnolog\u00eda e Innovaci\u00f3n (CITIUS)"},{"name":"Biointeractomics Platform (cic-Cartuja), Funda\u00e7\u00e3o para a Ci\u00eancia e Tecnologia, Portugal","award":["PEST-OE\/EQB\/LA0004\/2013"],"award-info":[{"award-number":["PEST-OE\/EQB\/LA0004\/2013"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Chemistry A European J"],"published-print":{"date-parts":[[2015,10,12]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Phosphorylation of tyrosine\u200548 of cytochrome\u2005<jats:italic>c<\/jats:italic> is related to a wide range of human diseases due to the pleiotropic role of the heme\u2010protein in cell life and death. However, the structural conformation and physicochemical properties of phosphorylated cytochrome\u2005<jats:italic>c<\/jats:italic> are difficult to study as its yield from cell extracts is very low and its kinase remains unknown. Herein, we report a high\u2010yielding synthesis of a close mimic of phosphorylated cytochrome\u2005<jats:italic>c<\/jats:italic>, developed by optimization of the synthesis of the non\u2010canonical amino acid <jats:italic>p<\/jats:italic>\u2010carboxymethyl\u2010<jats:sc>L<\/jats:sc>\u2010phenylalanine (<jats:italic>p<\/jats:italic>CMF) and its efficient site\u2010specific incorporation at position 48. It is noteworthy that the Y48<jats:italic>p<\/jats:italic>CMF mutation significantly destabilizes the Fe\uf8ffMet bond in the ferric form of cytochrome\u2005<jats:italic>c<\/jats:italic>, thereby lowering the p<jats:italic>K<\/jats:italic><jats:sub>a<\/jats:sub> value for the alkaline transition of the heme\u2010protein. This finding reveals the differential ability of the phosphomimic protein to drive certain events. This modified cytochrome\u2005<jats:italic>c<\/jats:italic> might be an important tool to investigate the role of the natural protein following phosphorylation.<\/jats:p>","DOI":"10.1002\/chem.201502019","type":"journal-article","created":{"date-parts":[[2015,8,28]],"date-time":"2015-08-28T11:30:49Z","timestamp":1440761449000},"page":"15004-15012","source":"Crossref","is-referenced-by-count":45,"title":["Mimicking Tyrosine Phosphorylation in Human Cytochrome\u2005<i>c<\/i> by the Evolved tRNA Synthetase Technique"],"prefix":"10.1002","volume":"21","author":[{"given":"Alejandra","family":"Guerra\u2010Castellano","sequence":"first","affiliation":[]},{"given":"Antonio","family":"D\u00edaz\u2010Quintana","sequence":"additional","affiliation":[]},{"given":"Blas","family":"Moreno\u2010Beltr\u00e1n","sequence":"additional","affiliation":[]},{"given":"Javier","family":"L\u00f3pez\u2010Prados","sequence":"additional","affiliation":[]},{"given":"Pedro M.","family":"Nieto","sequence":"additional","affiliation":[]},{"given":"Wiebke","family":"Meister","sequence":"additional","affiliation":[]},{"given":"Jana","family":"Staffa","sequence":"additional","affiliation":[]},{"given":"Miguel","family":"Teixeira","sequence":"additional","affiliation":[]},{"given":"Peter","family":"Hildebrandt","sequence":"additional","affiliation":[]},{"given":"Miguel A.","family":"De\u2005la\u2005Rosa","sequence":"additional","affiliation":[]},{"given":"Irene","family":"D\u00edaz\u2010Moreno","sequence":"additional","affiliation":[]}],"member":"311","published-online":{"date-parts":[[2015,8,21]]},"reference":[{"key":"e_1_2_6_1_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0006-291X(03)00814-3"},{"key":"e_1_2_6_2_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.niox.2006.06.004"},{"key":"e_1_2_6_3_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.niox.2008.04.014"},{"key":"e_1_2_6_4_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.mito.2011.01.010"},{"key":"e_1_2_6_5_2","doi-asserted-by":"publisher","DOI":"10.1016\/0891-5849(96)00051-2"},{"key":"e_1_2_6_6_2","doi-asserted-by":"publisher","DOI":"10.2741\/3569"},{"key":"e_1_2_6_7_2","doi-asserted-by":"publisher","DOI":"10.1111\/febs.12224"},{"key":"e_1_2_6_8_2","doi-asserted-by":"publisher","DOI":"10.1111\/j.1469-7793.2003.00335.x"},{"key":"e_1_2_6_9_2","doi-asserted-by":"publisher","DOI":"10.1007\/s10863-008-9169-3"},{"key":"e_1_2_6_10_2","doi-asserted-by":"publisher","DOI":"10.1007\/978-1-4614-3573-0_10"},{"key":"e_1_2_6_11_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0962-8924(00)01803-1"},{"key":"e_1_2_6_12_2","doi-asserted-by":"publisher","DOI":"10.1007\/s00425-008-0721-5"},{"key":"e_1_2_6_13_2","doi-asserted-by":"publisher","DOI":"10.1038\/nrm2434"},{"key":"e_1_2_6_14_2","doi-asserted-by":"publisher","DOI":"10.1074\/mcp.M113.034322"},{"key":"e_1_2_6_15_2","doi-asserted-by":"publisher","DOI":"10.1021\/bi801329s"},{"key":"e_1_2_6_16_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0076-6879(08)01211-1"},{"key":"e_1_2_6_17_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbabio.2010.03.009"},{"key":"e_1_2_6_18_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbabio.2011.09.012"},{"key":"e_1_2_6_19_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.febslet.2011.12.007"},{"key":"e_1_2_6_20_2","doi-asserted-by":"publisher","DOI":"10.1021\/bi060585v"},{"key":"e_1_2_6_21_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbamcr.2007.10.001"},{"key":"e_1_2_6_22_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbabio.2008.04.023"},{"key":"e_1_2_6_23_2","doi-asserted-by":"publisher","DOI":"10.1007\/BF00530744"},{"key":"e_1_2_6_24_2","doi-asserted-by":"publisher","DOI":"10.1021\/bi100486s"},{"key":"e_1_2_6_25_2","doi-asserted-by":"publisher","DOI":"10.1007\/s00775-011-0804-9"},{"key":"e_1_2_6_26_2","doi-asserted-by":"publisher","DOI":"10.1038\/nmeth864"},{"key":"e_1_2_6_27_2","doi-asserted-by":"publisher","DOI":"10.1021\/cb700083w"},{"key":"e_1_2_6_28_2","first-page":"550","volume":"45","author":"Radi R.","year":"2012","journal-title":"Acc. Chem. Res."},{"key":"e_1_2_6_29_2","doi-asserted-by":"publisher","DOI":"10.1021\/jm801332q"},{"key":"e_1_2_6_30_2","doi-asserted-by":"publisher","DOI":"10.1248\/cpb.29.1475"},{"key":"e_1_2_6_31_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0040-4039(01)91563-1"},{"key":"e_1_2_6_32_2","doi-asserted-by":"publisher","DOI":"10.1021\/jm00107a037"},{"key":"e_1_2_6_33_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0957-4166(00)82297-1"},{"key":"e_1_2_6_34_2","doi-asserted-by":"publisher","DOI":"10.1042\/BJ20130758"},{"key":"e_1_2_6_35_2","doi-asserted-by":"publisher","DOI":"10.1023\/A:1022561924392"},{"key":"e_1_2_6_36_2","doi-asserted-by":"publisher","DOI":"10.1002\/chem.201103413"},{"key":"e_1_2_6_37_2","doi-asserted-by":"publisher","DOI":"10.1093\/nar\/gkl282"},{"key":"e_1_2_6_38_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0162-0134(97)00100-1"},{"key":"e_1_2_6_39_2","doi-asserted-by":"publisher","DOI":"10.1021\/bi00077a021"},{"key":"e_1_2_6_40_2","doi-asserted-by":"publisher","DOI":"10.1529\/biophysj.107.116483"},{"key":"e_1_2_6_41_2","doi-asserted-by":"publisher","DOI":"10.1021\/jp802495q"},{"key":"e_1_2_6_42_2","doi-asserted-by":"publisher","DOI":"10.1021\/bi970724w"},{"key":"e_1_2_6_43_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0006-3495(01)76119-X"},{"key":"e_1_2_6_44_2","doi-asserted-by":"publisher","DOI":"10.1007\/s10863-009-9223-9"},{"key":"e_1_2_6_45_2","first-page":"611","volume-title":"Cytochrome\u2005C: A Multidisciplinary Approach","author":"Wilson M. T.","year":"1996"},{"key":"e_1_2_6_46_2","doi-asserted-by":"publisher","DOI":"10.1021\/ja027180s"},{"key":"e_1_2_6_47_2","doi-asserted-by":"publisher","DOI":"10.1021\/bi00896a006"},{"key":"e_1_2_6_48_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.0809279106"},{"key":"e_1_2_6_49_2","doi-asserted-by":"publisher","DOI":"10.1021\/ja00247a009"},{"key":"e_1_2_6_50_2","doi-asserted-by":"publisher","DOI":"10.1021\/jp302301m"},{"key":"e_1_2_6_51_2","doi-asserted-by":"publisher","DOI":"10.1007\/s007750050064"},{"key":"e_1_2_6_52_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.jmb.2003.09.070"},{"key":"e_1_2_6_53_2","doi-asserted-by":"publisher","DOI":"10.1002\/prot.20757"},{"key":"e_1_2_6_54_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.0813120106"},{"key":"e_1_2_6_55_2","doi-asserted-by":"publisher","DOI":"10.1529\/biophysj.106.095976"},{"key":"e_1_2_6_56_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0021-9258(19)44026-X"},{"key":"e_1_2_6_57_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbrc.2003.10.182"},{"key":"e_1_2_6_58_2","doi-asserted-by":"publisher","DOI":"10.1007\/s10858-012-9606-9"},{"key":"e_1_2_6_59_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.febslet.2015.01.004"},{"key":"e_1_2_6_60_2","doi-asserted-by":"publisher","DOI":"10.1006\/abbi.1995.1202"},{"key":"e_1_2_6_61_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbapap.2005.06.005"},{"key":"e_1_2_6_62_2","doi-asserted-by":"publisher","DOI":"10.1006\/abio.2000.4880"},{"key":"e_1_2_6_63_2","doi-asserted-by":"publisher","DOI":"10.1038\/nprot.2006.202"},{"key":"e_1_2_6_64_2","doi-asserted-by":"publisher","DOI":"10.1111\/j.1747-0285.2009.00847.x"},{"key":"e_1_2_6_65_2","first-page":"461","volume-title":"Principal Components Analysis and Receptor Models in Environmental Forensics, in Introduction to Environmental Forensics","author":"Johnson G. W.","year":"2002"},{"key":"e_1_2_6_66_2","doi-asserted-by":"publisher","DOI":"10.1021\/j150512a005"},{"key":"e_1_2_6_67_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0006-3495(90)82502-9"},{"key":"e_1_2_6_68_2","doi-asserted-by":"publisher","DOI":"10.1021\/cr00024a009"},{"key":"e_1_2_6_69_2","doi-asserted-by":"publisher","DOI":"10.1021\/ja00136a003"},{"key":"e_1_2_6_70_2","unstructured":"D.\u2005H. 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\u2010Ferrer C. Sagui V. Babin T. Luchko S. Gusarov A. Kovalenko P.\u2005A. Kollman AMBER\u200512 University of California San Francisco (USAm) 2012."},{"key":"e_1_2_6_71_2","doi-asserted-by":"publisher","DOI":"10.1021\/ja955032e"},{"key":"e_1_2_6_72_2","doi-asserted-by":"publisher","DOI":"10.1002\/jcc.20079"},{"key":"e_1_2_6_73_2","doi-asserted-by":"publisher","DOI":"10.1002\/jcc.540141112"},{"key":"e_1_2_6_74_2","doi-asserted-by":"publisher","DOI":"10.1093\/nar\/gkr288"},{"key":"e_1_2_6_75_2","first-page":"281","volume":"12","author":"Homeyer N.","year":"2006","journal-title":"J. Mol. Biol."}],"container-title":["Chemistry \u2013 A European Journal"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.wiley.com\/onlinelibrary\/tdm\/v1\/articles\/10.1002%2Fchem.201502019","content-type":"unspecified","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/chemistry-europe.onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/chem.201502019","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,12]],"date-time":"2025-10-12T10:38:56Z","timestamp":1760265536000},"score":1,"resource":{"primary":{"URL":"https:\/\/chemistry-europe.onlinelibrary.wiley.com\/doi\/10.1002\/chem.201502019"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2015,8,21]]},"references-count":75,"journal-issue":{"issue":"42","published-print":{"date-parts":[[2015,10,12]]}},"alternative-id":["10.1002\/chem.201502019"],"URL":"https:\/\/doi.org\/10.1002\/chem.201502019","archive":["Portico"],"relation":{},"ISSN":["0947-6539","1521-3765"],"issn-type":[{"value":"0947-6539","type":"print"},{"value":"1521-3765","type":"electronic"}],"subject":[],"published":{"date-parts":[[2015,8,21]]}}}