Octahedral Trifluoromagnesate, an Anomalous Metal Fluoride Species, Stabilizes the Transition State in a Biological Motor

Mengyu Ge; Molt Jr Robert W.; Huw T. Jenkins; G. Michael Blackburn; Yi Jin; Alfred A. Antson

doi:10.1021/acscatal.0c04500

Octahedral Trifluoromagnesate, an Anomalous Metal Fluoride Species, Stabilizes the Transition State in a Biological Motor

Mengyu Ge, Molt Jr Robert W., Huw T. Jenkins, G. Michael Blackburn, Yi Jin, Alfred A. Antson

Chemical Biology and Biological Chemistry

The University of Sheffield

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

Abstract

Isoelectronic metal fluoride transition state analogue (TSA) complexes, MgF₃^– and AlF₄^–, have proven to be immensely useful in understanding mechanisms of biological motors utilizing phosphoryl transfer. Here we report a previously unobserved octahedral TSA complex, MgF₃(H₂O)⁻, in a 1.5 Å resolution Zika virus NS3 helicase crystal structure. ¹⁹F NMR provided independent validation and also the direct observation of conformational tightening resulting from ssRNA binding in solution. The TSA stabilizes the two conformations of motif V of the helicase that link ATP hydrolysis with mechanical work. DFT analysis further validated the MgF₃(H₂O)⁻ species, indicating the significance of this TSA for studies of biological motors.

Original language	English
Pages (from-to)	2769-2773
Number of pages	5
Journal	ACS Catalysis
Volume	11
Issue number	5
Early online date	17 Feb 2021
DOIs	https://doi.org/10.1021/acscatal.0c04500
Publication status	Published - 5 Mar 2021

Keywords

virus helicase
transition state analogue
ATPase
19F NMR
protein crystallography
general base catalysis
phosphoryl transfer mechanism

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10.1021/acscatal.0c04500

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title = "Octahedral Trifluoromagnesate, an Anomalous Metal Fluoride Species, Stabilizes the Transition State in a Biological Motor",

abstract = "Isoelectronic metal fluoride transition state analogue (TSA) complexes, MgF3– and AlF4–, have proven to be immensely useful in understanding mechanisms of biological motors utilizing phosphoryl transfer. Here we report a previously unobserved octahedral TSA complex, MgF3(H2O)−, in a 1.5 {\AA} resolution Zika virus NS3 helicase crystal structure. 19F NMR provided independent validation and also the direct observation of conformational tightening resulting from ssRNA binding in solution. The TSA stabilizes the two conformations of motif V of the helicase that link ATP hydrolysis with mechanical work. DFT analysis further validated the MgF3(H2O)− species, indicating the significance of this TSA for studies of biological motors.",

keywords = "virus helicase, transition state analogue, ATPase, 19F NMR, protein crystallography, general base catalysis, phosphoryl transfer mechanism",

author = "Mengyu Ge and {Robert W.}, {Molt Jr} and Jenkins, {Huw T.} and Blackburn, {G. Michael} and Yi Jin and Antson, {Alfred A.}",

year = "2021",

month = mar,

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doi = "10.1021/acscatal.0c04500",

language = "English",

volume = "11",

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journal = "ACS Catalysis",

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TY - JOUR

T1 - Octahedral Trifluoromagnesate, an Anomalous Metal Fluoride Species, Stabilizes the Transition State in a Biological Motor

AU - Ge, Mengyu

AU - Robert W., Molt Jr

AU - Jenkins, Huw T.

AU - Blackburn, G. Michael

AU - Jin, Yi

AU - Antson, Alfred A.

PY - 2021/3/5

Y1 - 2021/3/5

N2 - Isoelectronic metal fluoride transition state analogue (TSA) complexes, MgF3– and AlF4–, have proven to be immensely useful in understanding mechanisms of biological motors utilizing phosphoryl transfer. Here we report a previously unobserved octahedral TSA complex, MgF3(H2O)−, in a 1.5 Å resolution Zika virus NS3 helicase crystal structure. 19F NMR provided independent validation and also the direct observation of conformational tightening resulting from ssRNA binding in solution. The TSA stabilizes the two conformations of motif V of the helicase that link ATP hydrolysis with mechanical work. DFT analysis further validated the MgF3(H2O)− species, indicating the significance of this TSA for studies of biological motors.

AB - Isoelectronic metal fluoride transition state analogue (TSA) complexes, MgF3– and AlF4–, have proven to be immensely useful in understanding mechanisms of biological motors utilizing phosphoryl transfer. Here we report a previously unobserved octahedral TSA complex, MgF3(H2O)−, in a 1.5 Å resolution Zika virus NS3 helicase crystal structure. 19F NMR provided independent validation and also the direct observation of conformational tightening resulting from ssRNA binding in solution. The TSA stabilizes the two conformations of motif V of the helicase that link ATP hydrolysis with mechanical work. DFT analysis further validated the MgF3(H2O)− species, indicating the significance of this TSA for studies of biological motors.

KW - virus helicase

KW - transition state analogue

KW - ATPase

KW - 19F NMR

KW - protein crystallography

KW - general base catalysis

KW - phosphoryl transfer mechanism

U2 - 10.1021/acscatal.0c04500

DO - 10.1021/acscatal.0c04500

M3 - Article

SN - 2155-5435

VL - 11

SP - 2769

EP - 2773

JO - ACS Catalysis

JF - ACS Catalysis

IS - 5

ER -

Octahedral Trifluoromagnesate, an Anomalous Metal Fluoride Species, Stabilizes the Transition State in a Biological Motor

Abstract

Keywords

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