Mapping molecular electrostatic potential for heme interacting with nano metal oxides

Interacting various living components with several materials in the gaseous nanoscale form has been of great concern as they are utilized in different life aspects. This work is conducted to assess the impact of interacting heme molecule, the main constituent of blood hemoglobin, with various common and non-common divalent molecules such as O2, CO2, CO, MgO, CoO, NiO, CuO and ZnO. Calculations are calculated at DFT high theoretical level using B3LYP/SDD method. In addition, molecular electrostatic potential (MESP) maps are constructed. Results demonstrate that interacting heme with proposed various structures lowers their energies reflecting more stability. However, the addition of non-familiar species to heme makes it more stable that may affect its transportation function for O2 and CO2 in the presence of these toxic materials in the gaseous state. The calculated TDM of the various proposed structures indicates that they are all more reactive than heme, since TDM of all of them are larger than that of pure heme. MESP maps show that extreme negative electrostatic regions are concentrated around C=O group of terminal carboxyl groups suggesting electrophilic interactions to take place there while positive regions are found around Fe central atom and on the circumference of all the proposed structures that are occupied by H atoms increasing the probability of nucleophilic reactions in these regions. Therefore, presence of such hazardous materials in the gaseous nanoscale may impact negatively the transportation function of heme.

Effect of nano metal oxides on heme molecule: molecular and biomolecular approaches

Interaction of components of living cells with various nanomaterials in the gas phase has been one of extensive concern since they become intensively utilized in various life aspects. This work is carried out to investigate the interaction between heme molecule, as the main component of hemoglobin, with several familiar and non-familiar divalent structures such as O2, CO2, CO, MgO, CoO, NiO, CuO and ZnO. Geometry optimization processes as well as QSAR descriptors are conducted using semiemprical quantum mechanical calculations at PM6 level. Results illustrate that adsorbing O2 and CO on heme lowers their TDM helping heme in performing its transportation function and not interacting with other species. On the other hand, when CoO and ZnO interacting with heme the TDM of the resultant structures increase greatly reflecting high reactivity which may interact with other species more than performing its function. Therefore, interacting species other than O2 may disturb the transportation function of heme structure. QSAR data of IP regarding interaction of O2 with heme ensure the TDM result that reflects lowering its activity. IP of H-CO adsorbed is the lowest indicating high reactivity while those of H-O2, H-CO2, H-MgO and H-NiO in the complex form are the highest values indicating that it is difficult to form a complex structure with them. Therefore, heme interactions with structures rather than O2 and CO2 affects negatively its function as gas transporter.

Crystal structure of heme A synthase from Bacillus subtilis

Heme A is an essential cofactor for respiratory terminal oxidases and vital for respiration in aerobic organisms. The final step of heme A biosynthesis is formylation of the C-8 methyl group of heme molecule by heme A synthase (HAS). HAS is a heme-containing integral membrane protein, and its structure and reaction mechanisms have remained unknown. Thus, little is known about HAS despite of its importance. Here we report the crystal structure of HAS from Bacillus subtilis at 2.2-Å resolution. The N- and C-terminal halves of HAS consist of four-helix bundles and they align in a pseudo twofold symmetry manner. Each bundle contains a pair of histidine residues and forms a heme-binding domain. The C-half domain binds a cofactor-heme molecule, while the N-half domain is vacant. Many water molecules are found in the transmembrane region and around the substrate-binding site, and some of them interact with the main chain of transmembrane helix. Comparison of these two domain structures enables us to construct a substrate-heme binding state structure. This structure implies that a completely conserved glutamate, Glu57 in B. subtilis, is the catalytic residue for the formylation reaction. These results provide valuable suggestions of the substrate-heme binding mechanism. Our results present significant insight into the heme A biosynthesis.