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.

The structure of Mycobacterium tuberculosis heme-degrading protein, MhuD, in complex with product

Mycobacterium tuberculosis (Mtb), the causative agent of tuberculosis, requires iron for survival. In Mtb, MhuD is the cytosolic protein that degrades imported heme. MhuD is distinct, both in sequence and structure, from canonical heme oxygenases (HOs) but homologous with IsdG-type proteins. Canonical HO is found mainly in eukaryotes, while IsdG-type proteins are predominantly found in prokaryotes including pathogens. While there are several published structures of MhuD and other IsdG-type proteins in complex with heme substrate, no structures have been reported of IsdG-type proteins in complex with product, unlike HOs. We recently showed that the Mtb variant MhuD-R26S produces biliverdin IXα (αBV) rather than the wild-type (WT) mycobilin isomers as product. Given that mycobilin and other IsdG-type protein products like staphylobilin are difficult to isolate in quantities sufficient for structure determination, here we use the MhuD-R26S variant and its product αBV as a proxy to study the IsdG-type protein/product complex. First we show that αBV has nanomolar affinity for MhuD and the R26S variant. Second we determined the MhuD-R26S-αBV complex structure to 2.5 Å, which reveals two notable features (1) two αBV molecules bound per active site and (2) a new α-helix (α3) as compared with the MhuD-heme structure. Finally, by molecular dynamics simulations we show that α3 is stable with the proximal αBV alone. MhuD’s high affinity for its product and structural and electrostatic changes that accompany substrate turnover suggest that there is an unidentified protein that is responsible for product extraction from MhuD and other IsdG-type proteins.

X-ray snapshots reveal conformational influence on active site ligation during metalloprotein folding

Parameters of local heme structure and overall conformation are tracked to reveal conformational influences on ligation states.