Phenylalanine hydroxylase catalyzes a critical step in the phenylalanine catabolic pathway, and impairment of the human enzyme is linked to phenylketonuria. Phenylalanine is also a positive allosteric regulator of the enzyme, and the allosteric binding site has been determined by crystallography. However, the allosteric activation mechanism remains unclear. Using large-scale simulations to explore how phenylalanine binds to the regulatory site, Ge et al. discovered gating motions of the protein that suggest a conformational selection mechanism.
Konovalov, K. A., Wang, W., & Huang, X. (2018). Conformational selection turns on phenylalanine hydroxylase. Journal of Biological Chemistry, 293(51), 19544–19545. doi:10.1074/jbc.h118.006676
This work was supported by the Hong Kong Research Grant Council (HKUST C6009-15G, 16307718, 16318816, and AoE/M-09/12) and King Abdullah University of Science and Technology (KAUST) Office of Sponsored Research (OSR) (OSR-2016-CRG5-3007). The authors declare that they have no conflicts of interest with the contents of this article.; Recipient of Hong Kong Ph.D. Fellowship Scheme PF16-06144.