Insights into the structural determinants of substrate specificity and activity in mouse aldehyde oxidases

• Type: Article in International Scientific Journal
• Date: 2015

Authors

Nuno M F S A Cerqueira (Author) Other; Catarina Coelho (Author) Other; Natercia F Bras (Author) Other; Pedro A Fernandes (Author) FCUP; Enrico Garattini (Author) Other; Mineko Terao (Author) Other; Maria Joao Romao (Author) Other; Maria Joao Ramos (Author) FCUP

Journal

Title: Journal of Biological Inorganic Chemistry

Vol. 20

Pages: 209-217

ISSN: 0949-8257

Publisher: Springer Nature

Indexing

ISI Web of Knowledge - 20 Citations

Scopus - 20 Citations

Scientific classification

FOS: Natural sciences > Chemical sciences

Other information

Authenticus ID: P-00A-BVH

DOI: 10.1007/s00775-014-1198-2

Abstract (EN): In this work, a combination of homology modeling and molecular dynamics (MD) simulations was used to investigate the factors that modulate substrate specificity and activity of the mouse AOX isoforms: mAOX1, mAOX2 (previously mAOX3l1), mAOX3 and mAOX4. The results indicate that the AOX isoform structures are highly preserved and even more conserved than the corresponding amino acid sequences. The only differences are at the protein surface and substrate-binding site region. The substrate-binding site of all isoforms consists of two regions: the active site, which is highly conserved among all isoforms, and a isoform-specific region located above. We predict that mAOX1 accepts a broader range of substrates of different shape, size and nature relative to the other isoforms. In contrast, mAOX4 appears to accept a more restricted range of substrates. Its narrow and hydrophobic binding site indicates that it only accepts small hydrophobic substrates. Although mAOX2 and mAOX3 are very similar to each other, we propose the following pairs of overlapping substrate specificities: mAOX2/mAOX4 and mAOX3/mAXO1. Based on these considerations, we propose that the catalytic activity between all isoforms should be similar but the differences observed in the binding site might influence the substrate specificity of each enzyme. These results also suggest that the presence of several AOX isoforms in mouse allows them to oxidize more efficiently a wider range of substrates. This contrasts with the same or other organisms that only express one isoform and are less efficient or incapable of oxidizing the same type of substrates.

Language: English

Type (Professor's evaluation): Scientific

No. of pages: 9