000117390 001__ 117390
000117390 005__ 20240319080952.0
000117390 0247_ $$2doi$$a10.1002/1873-3468.14238
000117390 0248_ $$2sideral$$a127396
000117390 037__ $$aART-2022-127396
000117390 041__ $$aeng
000117390 100__ $$aPacheco-Garcia J.L.
000117390 245__ $$aA single evolutionarily divergent mutation determines the different FAD-binding affinities of human and rat NQO1 due to site-specific phosphorylation
000117390 260__ $$c2022
000117390 5060_ $$aAccess copy available to the general public$$fUnrestricted
000117390 5203_ $$aThe phosphomimetic mutation S82D in the cancer-associated, FAD-dependent human NADP(H):quinone oxidoreductase 1 (hNQO1) causes a decrease in flavin-adenine dinucleotide-binding affinity and intracellular stability. We test in this work whether the evolutionarily recent neutral mutation R80H in the vicinity of S82 may alter the strong functional effects of S82 phosphorylation through electrostatic interactions. We show using biophysical and bioinformatic analyses that the reverse mutation H80R prevents the effects of S82D phosphorylation on hNQO1 by modulating the local stability. Consistently, in rat NQO1 (rNQO1) which contains R80, the effects of phosphorylation were milder, resembling the behaviour found in hNQO1 when this residue was humanized in rNQO1 (by the R80H mutation). Thus, apparently neutral and evolutionarily divergent mutations may determine the functional response of mammalian orthologues towards phosphorylation. © 2021 The Authors. FEBS Letters published by John Wiley & Sons Ltd on behalf of Federation of European Biochemical Societies
000117390 536__ $$9info:eu-repo/grantAgreement/ES/MCIU-AEI-FEDER/RTI2018-097991-B-I00$$9info:eu-repo/grantAgreement/ES/MCIU-ERDF/RTI2018-096246-B-I00
000117390 540__ $$9info:eu-repo/semantics/openAccess$$aby$$uhttp://creativecommons.org/licenses/by/3.0/es/
000117390 590__ $$a3.5$$b2022
000117390 591__ $$aBIOPHYSICS$$b21 / 70 = 0.3$$c2022$$dQ2$$eT1
000117390 591__ $$aCELL BIOLOGY$$b121 / 191 = 0.634$$c2022$$dQ3$$eT2
000117390 591__ $$aBIOCHEMISTRY & MOLECULAR BIOLOGY$$b150 / 285 = 0.526$$c2022$$dQ3$$eT2
000117390 594__ $$a7.0$$b2022
000117390 592__ $$a1.276$$b2022
000117390 593__ $$aBiophysics$$c2022$$dQ1
000117390 593__ $$aGenetics$$c2022$$dQ1
000117390 593__ $$aBiochemistry$$c2022$$dQ1
000117390 593__ $$aMolecular Biology$$c2022$$dQ2
000117390 593__ $$aStructural Biology$$c2022$$dQ2
000117390 593__ $$aCell Biology$$c2022$$dQ2
000117390 655_4 $$ainfo:eu-repo/semantics/article$$vinfo:eu-repo/semantics/publishedVersion
000117390 700__ $$aLoginov D.
000117390 700__ $$aRizzuti B.
000117390 700__ $$aVankova P.
000117390 700__ $$aNeira J.L.
000117390 700__ $$aKavan D.
000117390 700__ $$aMesa-Torres N.
000117390 700__ $$aGuzzi R.
000117390 700__ $$aMan P.
000117390 700__ $$aPey A.L.
000117390 773__ $$g596, 1 (2022), 29-41$$pFEBS lett.$$tFEBS Letters$$x0014-5793
000117390 8564_ $$s5597210$$uhttps://zaguan.unizar.es/record/117390/files/texto_completo.pdf$$yVersión publicada
000117390 8564_ $$s2390463$$uhttps://zaguan.unizar.es/record/117390/files/texto_completo.jpg?subformat=icon$$xicon$$yVersión publicada
000117390 909CO $$ooai:zaguan.unizar.es:117390$$particulos$$pdriver
000117390 951__ $$a2024-03-18-13:09:29
000117390 980__ $$aARTICLE