Time-resolved crystallography reveals allosteric communication aligned with molecular breathing

Pedram Mehrabi; Eike C Schulz; Raison Dsouza; Henrike M Müller-Werkmeister; Friedjof Tellkamp; R J Dwayne Miller; Emil F Pai

doi:10.1126/science.aaw9904

Time-resolved crystallography reveals allosteric communication aligned with molecular breathing

Standard

Time-resolved crystallography reveals allosteric communication aligned with molecular breathing. / Mehrabi, Pedram; Schulz, Eike C; Dsouza, Raison; Müller-Werkmeister, Henrike M; Tellkamp, Friedjof; Miller, R J Dwayne; Pai, Emil F.

In: SCIENCE, Vol. 365, No. 6458, 13.09.2019, p. 1167-1170.

Research output: SCORING: Contribution to journal › SCORING: Journal article › Research › peer-review

Harvard

Mehrabi, P, Schulz, EC, Dsouza, R, Müller-Werkmeister, HM, Tellkamp, F, Miller, RJD & Pai, EF 2019, 'Time-resolved crystallography reveals allosteric communication aligned with molecular breathing', SCIENCE, vol. 365, no. 6458, pp. 1167-1170. https://doi.org/10.1126/science.aaw9904

APA

Mehrabi, P., Schulz, E. C., Dsouza, R., Müller-Werkmeister, H. M., Tellkamp, F., Miller, R. J. D., & Pai, E. F. (2019). Time-resolved crystallography reveals allosteric communication aligned with molecular breathing. SCIENCE, 365(6458), 1167-1170. https://doi.org/10.1126/science.aaw9904

Vancouver

Mehrabi P, Schulz EC, Dsouza R, Müller-Werkmeister HM, Tellkamp F, Miller RJD et al. Time-resolved crystallography reveals allosteric communication aligned with molecular breathing. SCIENCE. 2019 Sep 13;365(6458):1167-1170. https://doi.org/10.1126/science.aaw9904

Bibtex

@article{4d0c1661dc1045afac4478810187bb4f,

title = "Time-resolved crystallography reveals allosteric communication aligned with molecular breathing",

abstract = "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.",

keywords = "Bacterial Proteins/chemistry, Catalysis, Catalytic Domain, Entropy, Hydrolases/chemistry, Kinetics, Ligands, Models, Molecular, Protein Conformation, Protein Multimerization, Rhodopseudomonas/enzymology",

author = "Pedram Mehrabi and Schulz, {Eike C} and Raison Dsouza and M{\"u}ller-Werkmeister, {Henrike M} and Friedjof Tellkamp and Miller, {R J Dwayne} and Pai, {Emil F}",

note = "Copyright {\textcopyright} 2019 The Authors, some rights reserved; exclusive licensee American Association for the Advancement of Science. No claim to original U.S. Government Works.",

year = "2019",

month = sep,

day = "13",

doi = "10.1126/science.aaw9904",

language = "English",

volume = "365",

pages = "1167--1170",

journal = "SCIENCE",

issn = "0036-8075",

publisher = "American Association for the Advancement of Science",

number = "6458",

}

RIS

TY - JOUR

T1 - Time-resolved crystallography reveals allosteric communication aligned with molecular breathing

AU - Mehrabi, Pedram

AU - Schulz, Eike C

AU - Dsouza, Raison

AU - Müller-Werkmeister, Henrike M

AU - Tellkamp, Friedjof

AU - Miller, R J Dwayne

AU - Pai, Emil F

PY - 2019/9/13

Y1 - 2019/9/13

N2 - 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.

AB - 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.

KW - Bacterial Proteins/chemistry

KW - Catalysis

KW - Catalytic Domain

KW - Entropy

KW - Hydrolases/chemistry

KW - Kinetics

KW - Ligands

KW - Models, Molecular

KW - Protein Conformation

KW - Protein Multimerization

KW - Rhodopseudomonas/enzymology

U2 - 10.1126/science.aaw9904

DO - 10.1126/science.aaw9904

M3 - SCORING: Journal article

C2 - 31515393

VL - 365

SP - 1167

EP - 1170

JO - SCIENCE

JF - SCIENCE

SN - 0036-8075

IS - 6458

ER -