Nitric oxide blocks cellular heme insertion into a broad range of heme proteins |
| |
| Authors: | Syed Mohsin Waheed Arnab Ghosh Ritu Chakravarti Ashis Biswas Mohammad Mahfuzul Haque Koustubh Panda Dennis J Stuehr |
| |
| Institution: | 1. Department of Pathobiology, Lerner Research Institute, The Cleveland Clinic, Cleveland, OH 44195, USA;2. Department of Chemistry, National Institute of Technology, Rourkela, India;3. Center for Genetic Engineering and Biotechnology, University of Calcutta, Kolkata, India;1. Department of Chemistry, Scripps Research Institute, 10550 North Torrey Pines Road, La Jolla, CA 92037, USA;2. Department of Molecular and Cell Biology, University of California, Berkeley, CA 94720, USA;3. Department of Chemistry, University of California, Berkeley, CA 94720, USA;1. Department of Pathobiology, Lerner Research Institute, 9500 Euclid Avenue, Cleveland Clinic, Cleveland, OH 44195, USA;2. School of Medicine, Case Western Reserve University, Cleveland, OH 44195, USA;1. Department of Biological Chemistry, Weizmann Institute of Science, Rehovot 7610001, Israel;2. Department of Structural Biology, Weizmann Institute of Science, Rehovot 7610001, Israel |
| |
| Abstract: | Although the insertion of heme into proteins enables their function in bioenergetics, metabolism, and signaling, the mechanisms and regulation of this process are not fully understood. We developed a means to study cellular heme insertion into apo-protein targets over a 3-h period and then investigated how nitric oxide (NO) released from a chemical donor (NOC-18) might influence heme (protoporphyrin IX) insertion into seven targets that present a range of protein structures, heme ligation states, and functions (three NO synthases, two cytochrome P450's, catalase, and hemoglobin). NO blocked cellular heme insertion into all seven apo-protein targets. The inhibition occurred at relatively low (nM/min) fluxes of NO, was reversible, and did not involve changes in intracellular heme levels, activation of guanylate cyclase, or inhibition of mitochondrial ATP production. These aspects and the range of protein targets suggest that NO can act as a global inhibitor of heme insertion, possibly by inhibiting a common step in the process. |
| |
| Keywords: | |
| 本文献已被 ScienceDirect 等数据库收录！ |
|
