Doing Chemistry with the Metal center in Proteins – Rational Design of Thermostable Metalloproteins

A large number of vital proteins and enzymes contain certain metal ion(s) or its complex bound to the protein at the active center. Our group has been involved in the study of the role of the metal ion and its surrounding environment on the structure, stability and function of the metalloprotein or metalloenzyme. The present talk will discuss our recent studies on the heme containing enzyme cytochrome P450 that is involved in drug metabolism, detoxification against xenobiotics, steroid biosynthesis etc. Rational design of the active site around the metal center in a thermostable cytochrome P450 was shown to catalyse reactions of unnatural substrates by the modified enzyme. The talk will also discuss studies on a novel purple copper center present in the ubiquitous respiratory enzyme cytochrome c oxidase. Selective modification of residues near the metal center was shown to alter the redox potential as well as electron transfer rates in this metal center that forms the electron entry site of cytochrome c oxidase. Mechanistic studies on the formation of the novel dinuclear copper center showed formation of two distinct kinetic intermediates containing mono-nuclear copper bound to the protein. These studies not only provide key insights on the biological functions of these important enzymes but also highlight their possible applications as potential thermostable green catalysts.