| Content Provider |
World Health Organization (WHO)-Global Index Medicus |
| Author |
Ahn, Young O. Gennis, Robert B. Lee, Hyun Ju Arjona, Davinia Rousseau, Denis L. Tajkhorshid, Emad Adelroth, Pia Ouyang, Hanlin Mahinthichaichan, Paween Kaluka, Daniel Yeh, Syun-ru |
| Description |
Author Affiliation: Ahn YO ( Department of Biochemistry, University of Illinois at Urbana-Champaign, Urbana, IL 61801); Mahinthichaichan P ( Department of Biochemistry, University of Illinois at Urbana-Champaign, Urbana, IL 61801); Lee HJ ( Department of Biochemistry and Biophysics, Arrhenius Laboratories for Natural Sciences, Stockholm University, SE-106 91 Stockholm, Sweden); Ouyang H ( Department of Biochemistry, University of Illinois at Urbana-Champaign, Urbana, IL 61801); Kaluka D ( Department of Physiology and Biophysics, Albert Einstein College of Medicine, Bronx, NY 10461.); Yeh SR ( Department of Physiology and Biophysics, Albert Einstein College of Medicine, Bronx, NY 10461.); Arjona D ( Department of Biochemistry and Biophysics, Arrhenius Laboratories for Natural Sciences, Stockholm University, SE-106 91 Stockholm, Sweden); Rousseau DL ( Department of Physiology and Biophysics, Albert Einstein College of Medicine, Bronx, NY 10461.); Tajkhorshid E ( Department of Biochemistry, University of Illinois at Urbana-Champaign, Urbana, IL 61801); Adelroth P ( Department of Biochemistry and Biophysics, Arrhenius Laboratories for Natural Sciences, Stockholm University, SE-106 91 Stockholm, Sweden); Gennis RB ( Department of Biochemistry, University of Illinois at Urbana-Champaign, Urbana, IL 61801); |
| Abstract |
The respiratory chains of nearly all aerobic organisms are terminated by proton-pumping heme-copper oxygen reductases (HCOs). Previous studies have established that C-family HCOs contain a single channel for uptake from the bacterial cytoplasm of all chemical and pumped protons, and that the entrance of the K(C)-channel is a conserved glutamate in subunit III. However, the majority of the K(C)-channel is within subunit I, and the pathway from this conserved glutamate to subunit I is not evident. In the present study, molecular dynamics simulations were used to characterize a chain of water molecules leading from the cytoplasmic solution, passing the conserved glutamate in subunit III and extending into subunit I. Formation of the water chain, which controls the delivery of protons to the K(C)-channel, was found to depend on the conformation of Y241(Vc), located in subunit I at the interface with subunit III. Mutations of Y241(Vc) (to A/F/H/S) in the Vibrio cholerae cbb3 eliminate catalytic activity, but also cause perturbations that propagate over a 28-Å distance to the active site heme b3. The data suggest a linkage between residues lining the K(C)-channel and the active site of the enzyme, possibly mediated by transmembrane helix 7, which contains both Y241(Vc) and the active site cross-linked Y255(Vc), as well as two CuB histidine ligands. Other mutations of residues within or near helix 7 also perturb the active site, indicating that this helix is involved in modulation of the active site of the enzyme. |
| ISSN |
00278424 |
| e-ISSN |
10916490 |
| Journal |
Proceedings of the National Academy of Sciences of the United States of America |
| Issue Number |
42 |
| Volume Number |
111 |
| Language |
English |
| Publisher |
National Academy of Sciences |
| Publisher Date |
2014-10-01 |
| Publisher Place |
United States |
| Access Restriction |
Open |
| Subject Keyword |
Bacterial Proteins Chemistry Electron Transport Complex IV Vibrio Cholerae Enzymology Catalytic Domain Copper Cytoplasm Metabolism Histidine Ligands Molecular Conformation Molecular Dynamics Simulation Mutagenesis, Site-Directed Mutation Oxygen Protein Conformation Protons Spectrophotometry, Ultraviolet Spectrum Analysis, Raman Research Support, N.I.H., Extramural Research Support, Non-U.S. Gov't Multidisciplinary |
| Content Type |
Text |
| Resource Type |
Article |
| Subject |
Multidisciplinary |
