Cytochromes P460 and c'-β: exploiting a novel fold for multiple functions

Area of Science:

• Biochemistry
• Structural Biology
• Enzymology

Background:

• Cytochromes P460 (cyts P460) and cytochromes c'-β (cyts c'-β) are structurally homologous heme c-containing proteins.
• Cyts P460 feature a unique heme-lysine cross-link, while cyts c'-β have a canonical c-heme.
• The cyt P460-cyt c'-β superfamily exhibits diverse heme environments and reactivities.

Purpose of the Study:

• To review the structural, spectroscopic, and enzymatic properties of the cyt P460-cyt c'-β superfamily.
• To understand the structural determinants of functional differences within this protein superfamily.

Main Methods:

• Literature review of structural, spectroscopic, and enzymatic studies.
• Comparative analysis of protein structures and heme environments.
• Examination of structure-function relationships.

Main Results:

• Cyts P460 with polar distal pockets oxidize NH₂OH to NO/N₂O via proton-coupled electron transfer.
• Cyts c'-β with hydrophobic distal pockets are proposed to function in gas binding.
• Intermediate proteins with mixed pocket characteristics present unresolved functions.

Conclusions:

• Structural variations in heme pocket polarity are key determinants of functional divergence in the cyt P460-cyt c'-β superfamily.
• Further research is needed to elucidate the functions of 'halfway house' proteins.