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 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.
Author details: | Pedram MehrabiORCiD, Eike C. SchulzORCiD, Raison DsouzaORCiD, Henrike Müller-WerkmeisterORCiDGND, Friedjof TellkampORCiD, R. J. Dwayne MillerORCiDGND, Emil F. PaiORCiD |
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DOI: | https://doi.org/10.1126/science.aaw9904 |
ISSN: | 0036-8075 |
ISSN: | 1095-9203 |
Pubmed ID: | https://pubmed.ncbi.nlm.nih.gov/31515393 |
Title of parent work (English): | Science |
Publisher: | American Assoc. for the Advancement of Science |
Place of publishing: | Washington |
Publication type: | Article |
Language: | English |
Year of first publication: | 2019 |
Publication year: | 2019 |
Release date: | 2020/11/24 |
Volume: | 365 |
Issue: | 6458 |
Number of pages: | 39 |
First page: | 1167 |
Last Page: | 1170 |
Funding institution: | Max Planck SocietyMax Planck SocietyFoundation CELLEX; Cluster of Excellence "The Hamburg Centre for Ultrafast Imaging" of the Deutsche Forschungsgemeinschaft (DFG)German Research Foundation (DFG) [EXC 1074, 194651731]; European UnionEuropean Union (EU) [623994]; Natural Sciences and Engineering Research Council of CanadaNatural Sciences and Engineering Research Council of Canada [RGPIN-2015-04877]; Canada Research Chairs programCanada Research Chairs; Burroughs Wellcome FundBurroughs Wellcome Fund; Alexander von Humboldt-StiftungAlexander von Humboldt Foundation |
Organizational units: | Mathematisch-Naturwissenschaftliche Fakultät / Institut für Physik und Astronomie |
DDC classification: | 5 Naturwissenschaften und Mathematik / 53 Physik / 530 Physik |
Peer review: | Referiert |