KAUST Grant NumberOSR-2016-CRG5-3007
Permanent link to this recordhttp://hdl.handle.net/10754/678619
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AbstractPhenylalanine 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.
CitationKonovalov, 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
SponsorsThis 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.
JournalJOURNAL OF BIOLOGICAL CHEMISTRY
PubMed Central IDPMC6314130
CollectionsPublications Acknowledging KAUST Support
- Towards the identification of the allosteric Phe-binding site in phenylalanine hydroxylase.
- Authors: Carluccio C, Fraternali F, Salvatore F, Fornili A, Zagari A
- Issue date: 2016
- Simulations of the regulatory ACT domain of human phenylalanine hydroxylase (PAH) unveil its mechanism of phenylalanine binding.
- Authors: Ge Y, Borne E, Stewart S, Hansen MR, Arturo EC, Jaffe EK, Voelz VA
- Issue date: 2018 Dec 21
- Structural basis for ligand-dependent dimerization of phenylalanine hydroxylase regulatory domain.
- Authors: Patel D, Kopec J, Fitzpatrick F, McCorvie TJ, Yue WW
- Issue date: 2016 Apr 6
- Identification of the Allosteric Site for Phenylalanine in Rat Phenylalanine Hydroxylase.
- Authors: Zhang S, Fitzpatrick PF
- Issue date: 2016 Apr 1
- Regulation of phenylalanine hydroxylase: conformational changes upon phenylalanine binding detected by hydrogen/deuterium exchange and mass spectrometry.
- Authors: Li J, Dangott LJ, Fitzpatrick PF
- Issue date: 2010 Apr 20