@misc{10481/72134,
year = {2021},
month = {11},
url = {http://hdl.handle.net/10481/72134},
abstract = {The phosphomimetic mutation S82D in the cancer-associated, FADdependent
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.},
organization = {Spanish Government},
organization = {European ERDF Funds (MCIU/AEI/FEDER, EU)	RTI2018-097991-BI00	
RTI2018-096246-B-I00},
organization = {FEDER/Junta de Andalucia-Consejeria de Transformacion Economica, Industria, Conocimiento y Universidades	P18-RT-2413},
organization = {EU Horizon 2020 project EU FT-ICR MS	731077},
organization = {Universidad de Granada/CBUA		
CZ.1.05/1.1.00/02.0109	
LM2018127 CIISB},
publisher = {John Wiley & Sons},
keywords = {Epistasis},
keywords = {Flavoprotein},
keywords = {Molecular evolution},
keywords = {Protein phosphorylation},
title = {A single evolutionarily divergent mutation determines the different FAD-binding affinities of human and rat NQO1 due to site-specific phosphorylation},
doi = {10.1002/1873-3468.14238},
author = {Pacheco García, Juan Luis and Mesa Torres, Noel and Pey Rodríguez, Ángel Luis},
}