2yld

Publication Abstract from PubMed

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 A 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 degrees ) 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 degrees ) 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 A 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.

Carbon monoxide poisoning is prevented by the energy costs of conformational changes in gas-binding haemproteins.,Antonyuk SV, Rustage N, Petersen CA, Arnst JL, Heyes DJ, Sharma R, Berry NG, Scrutton NS, Eady RR, Andrew CR, Hasnain SS Proc Natl Acad Sci U S A. 2011 Sep 20;108(38):15780-5. Epub 2011 Sep 7. PMID:21900609^[1]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.