A role of Gln596 in fine-tuning mammalian ALOX15 specificity, protein stability and allosteric properties

Biochimica Et Biophysica Acta. Molecular and Cell Biology of Lipids
Alejandro CruzIgor Ivanov

Abstract

His596 of human ALOX12 has been suggested to interact with the COO--group of arachidonic acid during ALOX catalysis. In mammalian ALOX15 orthologs Gln596 occupies this position and this amino acid exchange might contribute to the functional differences between the two ALOX-isoforms. To explore the role of Gln596 for ALOX15 functionality we mutated this amino acid to different residues in rabbit and human ALOX15 and investigated the impact of these mutations on structural, catalytic and allosteric enzyme properties. To shed light on the molecular basis of the observed functional alterations we performed in silico substrate docking studies and molecular dynamics simulations and also explored the impact of Gln596 exchange on the protein structure. The combined theoretical and experimental data suggest that Gln596 may not directly interact with the COO--group of arachidonic acid. In contrast, mutations at Gln596 destabilize the secondary and tertiary structure of ALOX15 orthologs, which may be related to a disturbance of the electrostatic interaction network with other amino acids in the immediate surrounding. Moreover, our MD-simulations suggest that the geometry of the dimer interface depends on the structure of substrate bound i...Continue Reading

References

Dec 15, 1988·Biochemical and Biophysical Research Communications·E SigalJ A Nadel
Jan 3, 1995·Biochimica Et Biophysica Acta·J Freire-MoarE Sigal
Jul 21, 1993·Biochimica Et Biophysica Acta·H KühnE Sigal
Mar 1, 1993·European Journal of Biochemistry·T WatanabeB Samuelsson
Apr 4, 1997·Journal of Molecular Biology·G JonesR Taylor
Apr 30, 2004·Journal of Computational Chemistry·Junmei WangDavid A Case
Jul 21, 2004·Journal of Computational Chemistry·Eric F PettersenThomas E Ferrin
May 12, 2005·The FEBS Journal·Igor IvanovHermann-Georg Holzhütter
Jun 28, 2005·Nucleic Acids Research·John C GordonAlexey Onufriev
Dec 23, 2009·The Journal of Biological Chemistry·Robert VogelMatthias Walther
May 3, 2011·Journal of Molecular Biology·Weifeng ShangEwa Skrzypczak-Jankun
Feb 27, 2013·Biochimica Et Biophysica Acta·Almerinda Di VenereIgor Ivanov
Mar 4, 2015·Archives of Biochemistry and Biophysics·Mária PekárováDagmar Heydeck
Jun 4, 2015·Proceedings of the National Academy of Sciences of the United States of America·András MicsonaiJózsef Kardos
Nov 18, 2015·Journal of Chemical Theory and Computation·James A MaierCarlos Simmerling
Sep 10, 2013·Journal of Chemical Theory and Computation·Romelia Salomon-FerrerRoss C Walker
Feb 26, 2016·Journal of Chemical Information and Modeling·Pengfei Li, Kenneth M Merz
Jan 2, 2019·Biochimica Et Biophysica Acta. Molecular and Cell Biology of Lipids·Nikita KozlovHartmut Kuhn

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Citations

Apr 4, 2021·International Journal of Molecular Sciences·Igor IvanovHartmut Kuhn

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