Double-lock ratchet mechanism revealing the role of alpha SER-344 in FoF1 ATP synthase
Artikel i vetenskaplig tidskrift, 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

Författare

Tamas Beke-Somfai

Chalmers, Kemi- och bioteknik, Fysikalisk kemi

Per Lincoln

Chalmers, Kemi- och bioteknik, Fysikalisk kemi

Bengt Nordén

Chalmers, Kemi- och bioteknik, Fysikalisk kemi

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

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

Vol. 108 12 4828-4833

Styrkeområden

Nanovetenskap och nanoteknik

Energi

Livsvetenskaper och teknik

Materialvetenskap

Ämneskategorier

Kemi

DOI

10.1073/pnas.1010453108

Mer information

Skapat

2017-10-07