Time-resolved crystallography reveals allosteric communication aligned with molecular breathing

A comprehensive understanding of protein function demands correlating structure and dynamic changes. Using time-resolved serial synchrotron crystallography, we visualized half-of-the-sites reactivity and correlated molecular-breathing motions in the enzyme fluoroacetate dehalogenase. Eighteen time p...

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Bibliographic Details
Published in:Science (American Association for the Advancement of Science) 2019-09, Vol.365 (6458), p.1167-1170
Main Authors: Mehrabi, Pedram, Schulz, Eike C, Dsouza, Raison, Müller-Werkmeister, Henrike M, Tellkamp, Friedjof, Miller, R J Dwayne, Pai, Emil F
Format: Article
Language:English
Subjects:
Allosteric properties
Bacterial Proteins - chemistry
Catalysis
Catalytic Domain
Crystallography
Dimers
Entropy
Enzymes
Hydrolases - chemistry
Kinetics
Ligands
Models, Molecular
Oligomers
Organic chemistry
Protein Conformation
Protein Multimerization
Protein structure
Proteins
Rhodopseudomonas - enzymology
Scientific Concepts
Structure-function relationships
Substrates
Water chemistry
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Summary:A comprehensive understanding of protein function demands correlating structure and dynamic changes. Using time-resolved serial synchrotron crystallography, we visualized half-of-the-sites reactivity and correlated molecular-breathing motions in the enzyme fluoroacetate dehalogenase. Eighteen time points from 30 milliseconds to 30 seconds cover four turnover cycles of the irreversible reaction. They reveal sequential substrate binding, covalent-intermediate formation, setup of a hydrolytic water molecule, and product release. Small structural changes of the protein mold and variations in the number and placement of water molecules accompany the various chemical steps of catalysis. Triggered by enzyme-ligand interactions, these repetitive changes in the protein framework's dynamics and entropy constitute crucial components of the catalytic machinery.
ISSN:0036-8075
1095-9203
DOI:10.1126/science.aaw9904