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Metalloprotein entatic control of ligand-metal bonds quantified by ultrafast x-ray spectroscopy

Mara, Michael W. and Hadt, Ryan G. and Reinhard, Marco Eli and Kroll, Thomas and Lim, Hyeongtaek and Hartsock, Robert W. and Alonso-Mori, Roberto and Chollet, Matthieu and Glownia, James M. and Nelson, Silke and Sokaras, Dimosthenis and Kunnus, Kristjan and Hodgson, Keith O. and Hedman, Britt and Bergmann, Uwe and Gaffney, Kelly J. and Solomon, Edward I. (2017) Metalloprotein entatic control of ligand-metal bonds quantified by ultrafast x-ray spectroscopy. Science, 356 (6344). pp. 1276-1280. ISSN 0036-8075. PMCID PMC5706643. doi:10.1126/science.aam6203.

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The multifunctional protein cytochrome c (cyt c) plays key roles in electron transport and apoptosis, switching function by modulating bonding between a heme iron and the sulfur in a methionine residue. This Fe-S(Met) bond is too weak to persist in the absence of protein constraints. We ruptured the bond in ferrous cyt c using an optical laser pulse and monitored the bond reformation within the protein active site using ultrafast x-ray pulses from an x-ray free-electron laser, determining that the Fe-S(Met) bond enthalpy is ~4 kcal/mol stronger than in the absence of protein constraints. The 4 kcal/mol is comparable with calculations of stabilization effects in other systems, demonstrating how biological systems use an entatic state for modest yet accessible energetics to modulate chemical function.

Item Type:Article
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URLURL TypeDescription CentralArticle Information
Hadt, Ryan G.0000-0001-6026-1358
Bergmann, Uwe0000-0001-5639-166X
Solomon, Edward I.0000-0003-0291-3199
Additional Information:© 2017 The Authors, some rights reserved; exclusive licensee American Association for the Advancement of Science. No claim to original U.S. Government Works. This is an article distributed under the terms of the Science Journals Default License. Received for publication December 19, 2016. Accepted for publication May 5, 2017. Use of the Linac Coherent Light Source (LCLS) and the Stanford Synchrotron Radiation Lightsource (SSRL) of the SLAC National Accelerator Laboratory is supported by the U.S. Department of Energy (DOE), Office of Science, Office of Basic Energy Sciences under contract DE-AC02-76SF00515. The SSRL Structural Molecular Biology Program is supported by the DOE Office of Biological and Environmental Research and by the National Institutes of Health, National Institute of General Medical Sciences (P41GM103393). This research was supported by the National Institute of General Medical Sciences of the National Institutes of Health under award R01GM040392 (E.I.S.). R.W.H., K.K., and K.J.G. acknowledge support from the Atomic, Molecular, and Optical Sciences program within the Chemical Sciences, Geosciences, and Biosciences Division of the Office of Basic Energy Sciences, Office of Science, DOE. M.E.R. acknowledges the Swiss National Science Foundation, project 158890. H.L. acknowledges an Abbott Laboratories graduate fellowship. R.G.H. is currently an Enrico Fermi Fellow at Argonne National Laboratory. All data are reported in the main text, figures, and supplementary material.
Funding AgencyGrant Number
Department of Energy (DOE)DE-AC02-76SF00515
Swiss National Science Foundation (SNSF)158890
Abbott LaboratoriesUNSPECIFIED
Argonne National LaboratoryUNSPECIFIED
Issue or Number:6344
PubMed Central ID:PMC5706643
Record Number:CaltechAUTHORS:20180612-094721524
Persistent URL:
Official Citation:Metalloprotein entatic control of ligand-metal bonds quantified by ultrafast x-ray spectroscopy BY MICHAEL W. MARA, RYAN G. HADT, MARCO ELI REINHARD, THOMAS KROLL, HYEONGTAEK LIM, ROBERT W. HARTSOCK, ROBERTO ALONSO-MORI, MATTHIEU CHOLLET, JAMES M. GLOWNIA, SILKE NELSON, DIMOSTHENIS SOKARAS, KRISTJAN KUNNUS, KEITH O. HODGSON, BRITT HEDMAN, UWE BERGMANN, KELLY J. GAFFNEY, EDWARD I. SOLOMON Science 23 Jun 2017: Vol. 356, Issue 6344, pp. 1276-1280 DOI: 10.1126/science.aam6203
Usage Policy:No commercial reproduction, distribution, display or performance rights in this work are provided.
ID Code:86997
Deposited By: George Porter
Deposited On:12 Jun 2018 17:27
Last Modified:15 Nov 2021 20:44

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