Conformational selection turns on phenylalanine hydroxylase

Kirill A. Konovalov; Wei Wang; Xuhui Huang

doi:10.1074/jbc.H118.006676

Conformational selection turns on phenylalanine hydroxylase

Kirill A. Konovalov, Wei Wang, Xuhui Huang

Research output: Contribution to journal › Article › peer-review

1 Scopus citations

Abstract

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.

Original language	English (US)
Pages (from-to)	19544-19545
Number of pages	2
Journal	Journal of Biological Chemistry
Volume	293
Issue number	51
DOIs	https://doi.org/10.1074/jbc.H118.006676
State	Published - Jan 4 2021
Externally published	Yes

Bibliographical note

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.

ASJC Scopus subject areas

Biochemistry
Cell Biology
Molecular Biology

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10.1074/jbc.H118.006676

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title = "Conformational selection turns on phenylalanine hydroxylase",

abstract = "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.",

author = "Konovalov, {Kirill A.} and Wei Wang and Xuhui Huang",

note = "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.",

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doi = "10.1074/jbc.H118.006676",

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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.

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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.

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EP - 19545

JO - Journal of Biological Chemistry

JF - Journal of Biological Chemistry

IS - 51

ER -

Conformational selection turns on phenylalanine hydroxylase

Abstract

Bibliographical note

ASJC Scopus subject areas

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