TY  - JOUR
PY  - 2011//
TI  - Carbon monoxide poisoning is prevented by the energy costs of conformational changes in gas-binding haemproteins
JO  - Proceedings of the National Academy of Sciences of the United States of America
A1  - Antonyuk, Svetlana V.
A1  - Rustage, Neil
A1  - Petersen, Christine A.
A1  - Arnst, Jamie L.
A1  - Heyes, Derren J.
A1  - Sharma, Raman
A1  - Berry, Neil G.
A1  - Scrutton, Nigel S.
A1  - Eady, Robert R.
A1  - Andrew, Colin R.
A1  - Hasnain, S. Samar
SP  - 15780
EP  - 15785
VL  - 108
IS  - 38
N2  - Carbon monoxide (CO) is a product of haem metabolism and organisms must evolve strategies to prevent endogenous CO poisoning of haemoproteins. We show that energy costs associated with conformational changes play a key role in preventing irreversible CO binding. AxCYTcp is a member of a family of haem proteins that form stable 5c-NO and 6c-CO complexes but do not form O(2) complexes. Structure of the AxCYTcp-CO complex at 1.25 Å resolution shows that CO binds in two conformations moderated by the extent of displacement of the distal residue Leu16 toward the haem 7-propionate. The presence of two CO conformations is confirmed by cryogenic resonance Raman data. The preferred linear Fe-C-O arrangement (170 ± 8°) is accompanied by a flip of the propionate from the distal to proximal face of the haem. In the second conformation, the Fe-C-O unit is bent (158 ± 8°) with no flip of propionate. The energetic cost of the CO-induced Leu-propionate movements is reflected in a 600 mV (57.9 kJmol(-1)) decrease in haem potential, a value in good agreement with density functional theory calculations. Substitution of Leu by Ala or Gly (structures determined at 1.03 and 1.04 Å resolutions) resulted in a haem site that binds CO in the linear mode only and where no significant change in redox potential is observed. Remarkably, these variants were isolated as ferrous 6c-CO complexes, attributable to the observed eight orders of magnitude increase in affinity for CO, including an approximately 10,000-fold decrease in the rate of dissociation. These new findings have wide implications for preventing CO poisoning of gas-binding haem proteins.<p />  <p>Language: en</p>
LA  - en
SN  - 0027-8424
UR  - http://dx.doi.org/10.1073/pnas.1109051108
ID  - ref1
ER  -