dc.contributor.author
Heydeck, Dagmar
dc.contributor.author
Reisch, Florian
dc.contributor.author
Schäfer, Marjann
dc.contributor.author
Kakularam, Kumar R.
dc.contributor.author
Roigas, Sophie A.
dc.contributor.author
Stehling, Sabine
dc.contributor.author
Püschel, Gerhard P.
dc.contributor.author
Kuhn, Hartmut
dc.date.accessioned
2023-01-27T09:46:17Z
dc.date.available
2023-01-27T09:46:17Z
dc.identifier.uri
https://refubium.fu-berlin.de/handle/fub188/37745
dc.identifier.uri
http://dx.doi.org/10.17169/refubium-37459
dc.description.abstract
Arachidonic acid lipoxygenases (ALOXs) have been implicated in the immune response of mammals. The reaction specificity of these enzymes is decisive for their biological functions and ALOX classification is based on this enzyme property. Comparing the amino acid sequences and the functional properties of selected mammalian ALOX15 orthologs we previously hypothesized that the reaction specificity of these enzymes can be predicted based on their amino acid sequences (Triad Concept) and that mammals, which are ranked in evolution below gibbons, express arachidonic acid 12-lipoxygenating ALOX15 orthologs. In contrast, Hominidae involving the great apes and humans possess 15-lipoxygenating enzymes (Evolutionary Hypothesis). These two hypotheses were based on sequence data of some 60 mammalian ALOX15 orthologs and about half of them were functionally characterized. Here, we compared the ALOX15 sequences of 152 mammals representing all major mammalian subclades expressed 44 novel ALOX15 orthologs and performed extensive mutagenesis studies of their triad determinants. We found that ALOX15 genes are absent in extant Prototheria but that corresponding enzymes frequently occur in Metatheria and Eutheria. More than 90% of them catalyze arachidonic acid 12-lipoxygenation and the Triad Concept is applicable to all of them. Mammals ranked in evolution above gibbons express arachidonic acid 15-lipoxygenating ALOX15 orthologs but enzymes with similar specificity are only present in less than 5% of mammals ranked below gibbons. This data suggests that ALOX15 orthologs have been introduced during Prototheria-Metatheria transition and put the Triad Concept and the Evolutionary Hypothesis on a much broader and more reliable experimental basis.
en
dc.rights.uri
https://creativecommons.org/licenses/by/4.0/
dc.subject
lipid peroxidation
en
dc.subject
oxidative stress
en
dc.subject
recombinant proteins
en
dc.subject.ddc
600 Technik, Medizin, angewandte Wissenschaften::610 Medizin und Gesundheit::610 Medizin und Gesundheit
dc.title
The Reaction Specificity of Mammalian ALOX15 Orthologs is Changed During Late Primate Evolution and These Alterations Might Offer Evolutionary Advantages for Hominidae
dc.type
Wissenschaftlicher Artikel
dcterms.bibliographicCitation.articlenumber
871585
dcterms.bibliographicCitation.doi
10.3389/fcell.2022.871585
dcterms.bibliographicCitation.journaltitle
Frontiers in Cell and Developmental Biology
dcterms.bibliographicCitation.originalpublishername
Frontiers Media SA
dcterms.bibliographicCitation.volume
10
refubium.affiliation
Charité - Universitätsmedizin Berlin
refubium.resourceType.isindependentpub
no
dcterms.accessRights.openaire
open access
dcterms.bibliographicCitation.pmid
35531094
dcterms.isPartOf.eissn
2296-634X