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

Tamas Beke-Somfai (Institutionen för kemi- och bioteknik, Fysikalisk kemi) ; Per Lincoln (Institutionen för kemi- och bioteknik, Fysikalisk kemi) ; Bengt Nordén (Institutionen för kemi- och bioteknik, Fysikalisk kemi)
Proceedings of the National Academy of Sciences of the United States of America (0027-8424). Vol. 108 (2011), 12, p. 4828-4833.
[Artikel, refereegranskad vetenskaplig]

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.

Nyckelord: quantum mechanics, reaction mechanism, molecular motor, bovine heart-mitochondria, catalytic sites, escherichia-coli, conformational change, rotational catalysis, enzymatic catalysis, qm/mm, methods, f-1-atpase, hydrolysis, resolution

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Denna post skapades 2011-04-14.
CPL Pubid: 139068


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Institutioner (Chalmers)

Institutionen för kemi- och bioteknik, Fysikalisk kemi (2005-2014)


Nanovetenskap och nanoteknik

Chalmers infrastruktur