Conformational Heterogeneity and Cooperative Effects of Mammalian ALOX15
Ivanov, Igor (MIREA-Russian Technological University. Lomonosov Institute of Fine Chemical Technologies)
Cruz Saez, Alejandro (Universitat Autònoma de Barcelona. Departament de Química)
Zhuravlev, Alexander (MIREA-Russian Technological University. Lomonosov Institute of Fine Chemical Technologies)
Di Venere, Almerinda (University of Tor Vergata. Department of Experimental Medicine)
Nicolai, Eleonora (University of Tor Vergata. Department of Experimental Medicine)
Stehling, Sabine (Charite-University Medicine Berlin. Institute of Biochemistry)
Osca Lluch, José María (Universitat Autònoma de Barcelona. Institut de Biotecnologia i de Biomedicina "Vicent Villar Palasí")
González-Lafont, Àngels (Universitat Autònoma de Barcelona. Institut de Biotecnologia i de Biomedicina "Vicent Villar Palasí")
Kuhn, Hartmut (Charite-University Medicine Berlin. Institute of Biochemistry)

Date:	2021
Abstract:	Arachidonic acid lipoxygenases (ALOXs) have been suggested to function as monomeric enzymes, but more recent data on rabbit ALOX15 indicated that there is a dynamic monomer-dimer equilibrium in aqueous solution. In the presence of an active site ligand (the ALOX15 inhibitor RS7) rabbit ALOX15 was crystalized as heterodimer and the X-ray coordinates of the two monomers within the dimer exhibit subtle structural differences. Using native polyacrylamide electrophoresis, we here observed that highly purified and predominantly monomeric rabbit ALOX15 and human ALOX15B are present in two conformers with distinct electrophoretic mobilities. In silico docking studies, molecular dynamics simulations, site directed mutagenesis experiments and kinetic measurements suggested that in aqueous solutions the two enzymes exhibit motional flexibility, which may impact the enzymatic properties.
Grants:	Agencia Estatal de Investigación CTQ2017-83745-P
Rights:	Aquest document està subjecte a una llicència d'ús Creative Commons. Es permet la reproducció total o parcial, la distribució, la comunicació pública de l'obra i la creació d'obres derivades, fins i tot amb finalitats comercials, sempre i quan es reconegui l'autoria de l'obra original.
Language:	Anglès
Document:	Article ; recerca ; Versió publicada
Subject:	Lipoxygenases ; Crystal structure ; Protein-protein interactions ; Cooperative effects ; Molecular dynamics
Published in:	International journal of molecular sciences, Vol. 22, Issue 6 (March 2021) , art. 3285, ISSN 1422-0067

DOI: 10.3390/ijms22063285
PMID: 33807076

18 p, 31.6 MB

The record appears in these collections:
Research literature > UAB research groups literature > Research Centres and Groups (research output) > Health sciences and biosciences > Institut de Biotecnologia i de Biomedicina (IBB)
Articles > Research articles
Articles > Published articles