Metalloprotein entatic control of ligand-metal bonds quantified by ultrafast x-ray spectroscopy.
Michael W MaraRyan G HadtMarco Eli ReinhardThomas KrollHyeongtaek LimRobert W HartsockRoberto Alonso-MoriMatthieu CholletJames M GlowniaSilke NelsonDimosthenis SokarasKristjan KunnusKeith O HodgsonBritt HedmanUwe BergmannKelly J GaffneyEdward I SolomonPublished in: Science (New York, N.Y.) (2018)
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.
Keyphrases
- high resolution
- amino acid
- protein protein
- binding protein
- electron transfer
- high speed
- oxidative stress
- magnetic resonance imaging
- dual energy
- molecular dynamics
- cell proliferation
- small molecule
- magnetic resonance
- single molecule
- cell death
- signaling pathway
- molecular dynamics simulations
- brain injury
- iron deficiency