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

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. As a result, 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.
Authors:
ORCiD logo [1] ; ORCiD logo [2] ;  [3] ;  [4] ; ORCiD logo [5] ;  [3] ;  [3] ;  [4] ;  [4] ; ORCiD logo [4] ; ORCiD logo [4] ;  [3] ; ORCiD logo [5] ;  [4] ;  [6] ; ORCiD logo [4] ; ORCiD logo [5]
  1. Stanford Univ., Stanford, CA (United States); SLAC National Accelerator Lab., Menlo Park, CA (United States); Univ. of California, Berkeley, CA (United States)
  2. Stanford Univ., Stanford, CA (United States); Argonne National Lab. (ANL), Lemont, IL (United States)
  3. Stanford Univ., Stanford, CA (United States). SLAC Accelerator Lab.
  4. Stanford Univ., Menlo Park, CA (United States). SLAC Accelerator Lab.
  5. Stanford Univ., Stanford, CA (United States); SLAC National Accelerator Lab., Menlo Park, CA (United States)
  6. Stanford Univ., Stanford, CA (United States). SLAC Accelerator Lab.; SLAC National Accelerator Lab., Menlo Park, CA (United States)
Publication Date:
Grant/Contract Number:
AC02-76SF00515; award290961; P41GM103393; award306971; R01GM040392; award301025
Type:
Accepted Manuscript
Journal Name:
Science
Additional Journal Information:
Journal Volume: 356; Journal Issue: 6344; Journal ID: ISSN 0036-8075
Publisher:
AAAS
Research Org:
SLAC National Accelerator Lab., Menlo Park, CA (United States)
Sponsoring Org:
USDOE
Country of Publication:
United States
Language:
English
Subject:
37 INORGANIC, ORGANIC, PHYSICAL, AND ANALYTICAL CHEMISTRY
OSTI Identifier:
1369315

Mara, Michael W., Hadt, Ryan G., Reinhard, Marco Eli, Kroll, Thomas, Lim, Hyeongtaek, Hartsock, Robert W., Alonso-Mori, Roberto, Chollet, Matthieu, Glownia, James M., Nelson, Silke, Sokaras, Dimosthenis, Kunnus, Kristjan, Hodgson, Keith O., Hedman, Britt, Bergmann, Uwe, Gaffney, Kelly J., and Solomon, Edward I.. Metalloprotein entatic control of ligand-metal bonds quantified by ultrafast x-ray spectroscopy. United States: N. p., Web. doi:10.1126/science.aam6203.
Mara, Michael W., Hadt, Ryan G., Reinhard, Marco Eli, Kroll, Thomas, Lim, Hyeongtaek, Hartsock, Robert W., Alonso-Mori, Roberto, Chollet, Matthieu, Glownia, James M., Nelson, Silke, Sokaras, Dimosthenis, Kunnus, Kristjan, Hodgson, Keith O., Hedman, Britt, Bergmann, Uwe, Gaffney, Kelly J., & Solomon, Edward I.. Metalloprotein entatic control of ligand-metal bonds quantified by ultrafast x-ray spectroscopy. United States. doi:10.1126/science.aam6203.
Mara, Michael W., Hadt, Ryan G., Reinhard, Marco Eli, Kroll, Thomas, Lim, Hyeongtaek, Hartsock, Robert W., Alonso-Mori, Roberto, Chollet, Matthieu, Glownia, James M., Nelson, Silke, Sokaras, Dimosthenis, Kunnus, Kristjan, Hodgson, Keith O., Hedman, Britt, Bergmann, Uwe, Gaffney, Kelly J., and Solomon, Edward I.. 2017. "Metalloprotein entatic control of ligand-metal bonds quantified by ultrafast x-ray spectroscopy". United States. doi:10.1126/science.aam6203. https://www.osti.gov/servlets/purl/1369315.
@article{osti_1369315,
title = {Metalloprotein entatic control of ligand-metal bonds quantified by ultrafast x-ray spectroscopy},
author = {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.},
abstractNote = {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. As a result, 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.},
doi = {10.1126/science.aam6203},
journal = {Science},
number = 6344,
volume = 356,
place = {United States},
year = {2017},
month = {6}
}