8JWK
The second purified state crystal structure of AKRtyl
Summary for 8JWK
| Entry DOI | 10.2210/pdb8jwk/pdb |
| Descriptor | Aldo/keto reductase, NADPH DIHYDRO-NICOTINAMIDE-ADENINE-DINUCLEOTIDE PHOSPHATE, 2-AMINO-2-HYDROXYMETHYL-PROPANE-1,3-DIOL, ... (4 entities in total) |
| Functional Keywords | aldo-keto reductase, oxidoreductase |
| Biological source | Streptomyces xinghaiensis |
| Total number of polymer chains | 16 |
| Total formula weight | 620035.92 |
| Authors | |
| Primary citation | Xiao, Z.,Zha, J.,Yang, X.,Huang, T.,Huang, S.,Liu, Q.,Wang, X.,Zhong, J.,Zheng, J.,Liang, R.,Deng, Z.,Zhang, J.,Lin, S.,Dai, S. A three-level regulatory mechanism of the aldo-keto reductase subfamily AKR12D. Nat Commun, 15:2128-2128, 2024 Cited by PubMed 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. PubMed: 38459030DOI: 10.1038/s41467-024-46363-z PDB entries with the same primary citation |
| Experimental method | X-RAY DIFFRACTION (2.32 Å) |
Structure validation
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