Truncated hemoglobins (trHbs) are widely distributed in bacteria and plants and have been found in some unicellular eukaryotes. Phylogenetic analysis based on protein sequences shows that trHbs branch into three groups, designated N (or I), O (or II), and P (or III). Most trHbs are involved in the O2/NO chemistry and/or oxidation/reduction function, permitting the survival of the microorganism in the host. Here, a detailed comparative analysis of kinetics and/or thermodynamics of (i) ferrous Mycobacterium tubertulosis trHbs N and O (Mt-trHbN and Mt-trHbO, respectively), and Campylobacter jejuni trHb (Cj-trHbP) nitrosylation, (ii) nitrite-mediated nitrosylation of ferrous Mt-trHbN, Mt-trHbO, and Cj-trHbP, and (iii) NO-based reductive nitrosylation of ferric Mt-trHbN, Mt-trHbO, and Cj-trHbP is reported. Ferrous and ferric Mt-trHbN and Cj-trHbP display a very high reactivity towards NO; however, the conversion of nitrite to NO is facilitated primarily by ferrous Mt-trHbN. Values of kinetic and/or thermodynamic parameters reflect specific trHb structural features, such as the ligand diffusion pathways to/from the heme, the heme distal pocket structure and polarity, and the ligand stabilization mechanisms. In particular, the high reactivity of Mt-trHbN and Cj-trHbP reflects the great ligand accessibility to the heme center by two protein matrix tunnels and the E7-path, respectively, and the penta-coordination of the heme-Fe atom. In contrast, the heme-Fe atom of Mt-trHbO the ligand accessibility to the heme center of Mt-trHbO needs large conformational readjustments, thus limiting the heme-based reactivity. These results agree with different roles of Mt-trHbN, Mt-trHbO, and Cj-trHbP in vivo.
Interdepartmental Laboratory of Electron Microscopy, University Roma Tre, Roma, Italy;Interdepartmental Laboratory of Electron Microscopy, University Roma Tre, Roma, Italy;Department of Sciences, University Roma Tre, Roma, Italy;Department of Clinical Sciences and Translational Medicine, University of Roma “Tor Vergata”, Roma, Italy;Interuniversity Consortium for the Research on the Chemistry of Metals in Biological Systems, Bari, Italy;Department of Physics, University of Genova, Genova, Italy;Interdepartmental Laboratory of Electron Microscopy, University Roma Tre, Roma, Italy;Department of Clinical Sciences and Translational Medicine, University of Roma “Tor Vergata”, Roma, Italy;Interuniversity Consortium for the Research on the Chemistry of Metals in Biological Systems, Bari, Italy
Recommended Citation:
Paolo Ascenzi,Alessandra di Masi,Grazia R. Tundo,et al. Nitrosylation Mechanisms of Mycobacterium tuberculosis and Campylobacter jejuni Truncated Hemoglobins N, O, and P[J]. PLOS ONE,2014-01-01,9(7)