This title appears in the Scientific Report : 2016 

Substrate Specificity, Inhibitor Selectivity and Structure-Function Relationships of Aldo-Keto Reductase 1B15: A Novel Human Retinaldehyde Reductase
Giménez-Dejoz, Joan
Kolář, Michal H. / Ruiz, Francesc X. / Crespo, Isidro / Cousido-Siah, Alexandra / Podjarny, Alberto / Barski, Oleg A. / Fanfrlík, Jindřich / Parés, Xavier / Farrés, Jaume (Corresponding author) / Porté, Sergio (Corresponding author)
Computational Biomedicine; IAS-5
Computational Biomedicine; INM-9
PLoS one, 10 (2015) 7, S. e0134506 -
Lawrence, Kan. PLoS 2015
10.1371/journal.pone.0134506
26222439
Journal Article
Theory, modelling and simulation
OpenAccess
OpenAccess
Please use the identifier: http://dx.doi.org/10.1371/journal.pone.0134506 in citations.
Please use the identifier: http://hdl.handle.net/2128/9847 in citations.
Human aldo-keto reductase 1B15 (AKR1B15) is a newly discovered enzyme which shares 92% amino acid sequence identity with AKR1B10. While AKR1B10 is a well characterized enzyme with high retinaldehyde reductase activity, involved in the development of several cancer types, the enzymatic activity and physiological role of AKR1B15 are still poorly known. Here, the purified recombinant enzyme has been subjected to substrate specificity characterization, kinetic analysis and inhibitor screening, combined with structural modeling. AKR1B15 is active towards a variety of carbonyl substrates, including retinoids, with lower kcat and Km values than AKR1B10. In contrast to AKR1B10, which strongly prefers all-trans-retinaldehyde, AKR1B15 exhibits superior catalytic efficiency with 9-cis-retinaldehyde, the best substrate found for this enzyme. With ketone and dicarbonyl substrates, AKR1B15 also shows higher catalytic activity than AKR1B10. Several typical AKR inhibitors do not significantly affect AKR1B15 activity. Amino acid substitutions clustered in loops A and C result in a smaller, more hydrophobic and more rigid active site in AKR1B15 compared with the AKR1B10 pocket, consistent with distinct substrate specificity and narrower inhibitor selectivity for AKR1B15.