The nature of the key reactive intermediates in heme catalysis

点击翻译按钮获取中文摘要

The involvement of the metallic element iron in various biological systems is well known. In many cases, iron is employed in the form of a heme group, most famously in hemoglobin. The family of catalytic heme proteins is vast, and the majority of these catalytic heme enzymes react with oxygen in an activation process that generates oxidised forms of the heme. These oxidised forms of heme are called Compound I (oxidised by two electrons) and Compound II (oxidised by one electron). They are such crucial intermediates in so many catalytic heme proteins - including many involved in drug metabolism and other biological oxidations - that the elucidation of their structure has become a fundamental question for all those in the field. Numerous attempts to establish the structure of Compound I and Compound II have, however, failed because of flaws in the methodology and the transient nature of the species. With improvements in methodology for neutron diffraction and for examination of iron-oxygen stretching frequencies for protein bands in crystallo (using on-line resonance Raman), it now becomes possible to take an alternative approach. We intend to use these new methods to establish, finally, the structures of these crucial intermediates.