Structure, spectra, and function of heme sites

Heme proteins are a class of biologically important macromolecules that hav e a unique, common active site, an iron-protoporphyrin IX complex. Despite the common active site, heme proteins have three distinct biological functi ons: reversible oxygen transport, reversible electron transfer, and metabol izing enzymes. Each type of heme protein differs in the specific forms of t he heme complexes that are involved in its biological function. Not only th e biological activity, but also the spectroscopic properties of the intact heme proteins are largely centered on the heme unit. Thus, for this family of proteins, there is a particularly strong Link between structure spectra and function. However, experimental spectroscopic methods cannot, by themse lves, yield a detailed molecular description of the heme active site in the many stable and transient forms that it assumes as a part of its function. Missing is a direct correspondence between observable properties and expli cit models for these diverse stable and transient forms of the heme active site that can best be provided by computational studies. In the work report ed here, the seminal role Flayed by one of these methods, the semiempirical all-valence electron INDO/SCF/CI method, developed in the laboratory of Dr . Michael Zerner, in elucidating the structure, spectra, and function of he me proteins is demonstrated by four examples from work done in our laborato ry. The goal of the first study was to elucidate the nature of the importan t oxyferrous species of the globins and to use it to provide a consistent e xplanation of the origin of the observed spectroscopic properties. The goal of the second study was to identify the origin of the signature spectrum o f the ubiquitous metabolizing heme proteins, the cytochrome P450s, an inten se peak at 450 nm giving them their name. The other two studies illustrate the usefulness of this method in identifying transient species in two relat ed families of metabolizing heme proteins. These are the postulated peroxid e complex of peroxidases and the putative catalytically active Compound 1 f orm of the cytochrome P450s. (C) 2000 John Wiley & Sons, Inc.