ArticleNature communications2024
A three-level regulatory mechanism of the aldo-keto reductase subfamily AKR12D.
Article in Nature communications, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 5 papers.
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Who cites it
5 citing papers in PubMed, 6 citations in OpenAlex.
- Targeted identification of new phaterpenes and elucidation of the relevant biosynthetic pathway inSynthetic and systems biotechnology · 2026Article
- Assessing the Performance of BioEmu in Understanding Protein Dynamics.International journal of molecular sciences · 2026Article
- Specialized aldo-keto reductases trigger complete degradation of mycotoxin deoxynivalenol.Nature communications · 2026Article
- Aldose reductase, fructose and fat production in the liver.The Biochemical journal · 2025Review
- Aldo-keto reductase (AKR) superfamily website and database: An update.Chemico-biological interactions · 2024Article
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Authors and funding
14 authors at 1 institution in 1 country.
Funding
Abstract
Modulation of protein function through allosteric regulation is central in biology, but biomacromolecular systems involving multiple subunits and ligands may exhibit complex regulatory mechanisms at different levels, which remain poorly understood. Here, we discover an aldo-keto reductase termed AKRtyl and present its three-level regulatory mechanism. Specifically, by combining steady-state and transient kinetics, X-ray crystallography and molecular dynamics simulation, we demonstrate that AKRtyl exhibits a positive synergy mediated by an unusual Monod-Wyman-Changeux (MWC) paradigm of allosteric regulation at low concentrations of the cofactor NADPH, but an inhibitory effect at high concentrations is observed. While the substrate tylosin binds at a remote allosteric site with positive cooperativity. We further reveal that these regulatory mechanisms are conserved in AKR12D subfamily, and that substrate cooperativity is common in AKRs across three kingdoms of life. This work provides an intriguing example for understanding complex allosteric regulatory networks.
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