TY - JOUR
T1 - Conformational selection turns on phenylalanine hydroxylase
AU - Konovalov, Kirill A.
AU - Wang, Wei
AU - Huang, Xuhui
N1 - KAUST Repository Item: Exported on 2022-06-07
Acknowledged KAUST grant number(s): OSR-2016-CRG5-3007
Acknowledgements: 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.
This publication acknowledges KAUST support, but has no KAUST affiliated authors.
PY - 2021/1/4
Y1 - 2021/1/4
N2 - 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.
AB - 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.
UR - http://hdl.handle.net/10754/678619
UR - https://linkinghub.elsevier.com/retrieve/pii/S0021925820310863
UR - http://www.scopus.com/inward/record.url?scp=85058919420&partnerID=8YFLogxK
U2 - 10.1074/jbc.H118.006676
DO - 10.1074/jbc.H118.006676
M3 - Article
C2 - 30578407
SN - 1083-351X
VL - 293
SP - 19544
EP - 19545
JO - Journal of Biological Chemistry
JF - Journal of Biological Chemistry
IS - 51
ER -