Heme: emergent roles of heme in signal transduction, functional regulation and as catalytic centres.

Protoporphyrin IX iron complex (heme) is an important cofactor for oxygen transfer, oxygen storage, oxygen activation, and electron transfer when bound to the heme proteins hemoglobin, myoglobin, cytochrome P450 and cytochrome c, respectively. In addition to these prototypical heme proteins, there are emergent, critical roles of exchangeable/labile heme in signal transduction. Specifically, it has been shown that association/dissociation of heme to/from heme-responsive sensors regulates numerous functions, including transcription, DNA binding, microRNA splicing, translation, protein kinase activity, protein degradation, heme degradation, K+ channel function, two-component signal transduction, and many other functions.

Kinetic analysis of a globin-coupled diguanylate cyclase, YddV: Effects of heme iron redox state, axial ligands, and heme distal mutations on catalysis.

Heme-based oxygen sensors allow bacteria to regulate their activity based on local oxygen levels. YddV, a globin-coupled oxygen sensor with diguanylate cyclase activity from Escherichia coli, regulates cyclic-di-GMP synthesis based on oxygen availability. Stable and active samples of the full-length YddV protein were prepared by attaching it to maltose binding protein (MBP).

Ellipticine-loaded apoferritin nanocarrier retains DNA adduct-based cytochrome P450-facilitated toxicity in neuroblastoma cells.

Although ellipticine (Elli) is an efficient anticancer agent, it exerts several adverse effects. One approach to decrease the adverse effects of drugs is their encapsulation inside a suitable nanocarrier, allowing targeted delivery to tumour tissue whereas avoiding healthy cells. We constructed a nanocarrier from apoferritin (Apo) bearing ellipticine, ApoElli, and subsequently characterized.

Coordination and redox state-dependent structural changes of the heme-based oxygen sensor GcHK associated with intraprotein signal transduction.

The heme-based oxygen sensor histidine kinase GcHK is part of a two-component signal transduction system in bacteria. O binding to the Fe(II) heme complex of its N-terminal globin domain strongly stimulates autophosphorylation at His in its C-terminal kinase domain. The 6-coordinate heme Fe(III)-OH and -CN complexes of GcHK are also active, but the 5-coordinate heme Fe(II) complex and the heme-free apo-form are inactive.