Architecture of the catalytic HPN motif is conserved in all E2 conjugating enzymes

The Biochemical Journal
Benjamin W Cook, Gary S Shaw

Abstract

E2 conjugating enzymes are the central enzymes in the ubiquitination pathway and are responsible for the transfer of ubiquitin and ubiquitin-like proteins on to target substrates. The secondary structural elements of the catalytic domain of these enzymes is highly conserved, including the sequence conservation of a three-residue HPN (His-Pro-Asn) motif located upstream of the active-site cysteine residue used for ubiquitin conjugation. Despite the vast structural knowledge of E2 enzymes, the catalytic mechanism of these enzymes remains poorly understood, in large part due to variation in the arrangements of the residues in the HPN motif in existing E2 structures. In the present study, we used the E2 enzyme HIP2 to probe the structures of the HPN motif in several other E2 enzymes. A combination of chemical-shift analysis, determination of the histidine protonation states and amide temperature coefficients were used to determine the orientation of the histidine ring and hydrogen-bonding arrangements within the HPN motif. Unlike many three-dimensional structures, we found that a conserved hydrogen bond between the histidine imidazole ring and the asparagine backbone amide proton, a common histidine protonation state, and a common ...Continue Reading

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Citations

Feb 19, 2016·Chemical Reviews·Elena PapaleoRuth Nussinov
May 8, 2015·Biomolecular NMR Assignments·D Reid PutneyNathan T Wright
Jun 22, 2017·Physical Chemistry Chemical Physics : PCCP·Woon Yong SohnMichel Mons
May 5, 2018·Scientific Reports·Manoj K RoutLeo Spyracopoulos
May 10, 2019·Journal of Computational Chemistry·Walker M JonesIsaiah Sumner
Oct 13, 2016·The Biochemical Journal·Arno F AlpiHelen Walden
Oct 18, 2020·Biomolecules·Sayanika BanerjeeReuven Wiener
Feb 27, 2020·Biophysical Journal·Benjamin W CookGary S Shaw
Feb 25, 2017·Chemical Reviews·Laurent Cappadocia, Christopher D Lima
Apr 8, 2014·Journal of Chemical Information and Modeling·Matteo TibertiElena Papaleo
Nov 26, 2014·Journal of the American Chemical Society·Manoj K RoutLeo Spyracopoulos

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