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Conformational Ensembles from Experimental Data
and Computer Simulations
Poster Abstracts
89
54-POS
Board 14
Structural and Mechanistic Insights into the Ε Subunit from Bacterial ATP Synthases
Alexander Krah
, Changbong Hyeon.
Korea Institute for Advanced Study (KIAS), Seoul, South Korea.
The central energy conversion machinery in all living cells, the ATP synthase, uses an
electrochemical ion gradient to synthesize ATP, the main energy source in all living cells, by a
catalytic rotational motion. Vice versa it can pump protons, by hydrolyzing ATP, rotating in the
opposite direction. The ε subunit from bacterial ATP synthases undergoes a large conformational
change from the ATPase inhibitory up- to the non-inhibitory down state upon ATP binding.
However, the ATP binding affinity of ε subunits from different organisms is dramatically
different, from 4 μM (thermophilic
Bacillus
PS3) to 20 mM (
Escherichia coli
), while others may
not bind ATP at all (e.g.
Mycobacterium tuberculosis
). We use MD simulations to clarify
reasons for the different ligand binding affinities of the ε subunit from different organisms. In
this work, we obtain the ATP binding site structure of the ε subunit from
Escherichia coli
,
deriving molecular reasons for the dramatically decreased binding affinity compared to the ε
subunit from thermophilic
Bacillus
PS3. Furthermore, we observe that the protonation state of
one carboxylate group is essential to allow ATP binding, inducing a conformational change and
ATP binding of one of the key binding residues - thus the mechanistic modes of the ε subunit
from distinct bacterial organisms are controlled differently.