Double-lock ratchet mechanism revealing the role of alpha SER-344 in FoF1 ATP synthase
Journal article, 2011

In a majority of living organisms, FoF1 ATP synthase performs the fundamental process of ATP synthesis. Despite the simple net reaction formula, ADP + Pi. ATP + H2O, the detailed step-by-step mechanism of the reaction yet remains to be resolved owing to the complexity of this multisubunit enzyme. Based on quantum mechanical computations using recent high resolution X-ray structures, we propose that during ATP synthesis the enzyme first prepares the inorganic phosphate for the gamma P-O-ADP bond-forming step via a double-proton transfer. At this step, the highly conserved alpha S344 side chain plays a catalytic role. The reaction thereafter progresses through another transition state (TS) having a planar PO3- ion configuration to finally form ATP. These two TSs are concluded crucial for ATP synthesis. Using stepwise scans and several models of the nucleotide-bound active site, some of the most important conformational changes were traced toward direction of synthesis. Interestingly, as the active site geometry progresses toward the ATP-favoring tight binding site, at both of these TSs, a dramatic increase in barrier heights is observed for the reverse direction, i.e., hydrolysis of ATP. This change could indicate a "ratchet" mechanism for the enzyme to ensure efficacy of ATP synthesis by shifting residue conformation and thus locking access to the crucial TSs.

qm/mm

resolution

reaction mechanism

bovine heart-mitochondria

hydrolysis

quantum mechanics

rotational catalysis

catalytic sites

f-1-atpase

conformational change

molecular motor

methods

enzymatic catalysis

escherichia-coli

Author

Tamas Beke-Somfai

Chalmers, Chemical and Biological Engineering, Physical Chemistry

Per Lincoln

Chalmers, Chemical and Biological Engineering, Physical Chemistry

Bengt Nordén

Chalmers, Chemical and Biological Engineering, Physical Chemistry

Proceedings of the National Academy of Sciences of the United States of America

0027-8424 (ISSN) 1091-6490 (eISSN)

Vol. 108 12 4828-4833

Areas of Advance

Nanoscience and Nanotechnology

Energy

Life Science Engineering

Materials Science

Subject Categories

Chemical Sciences

DOI

10.1073/pnas.1010453108

More information

Created

10/7/2017