Paul Ortiz de Montellano, PhD

What I do

My laboratory investigates the mechanisms of heme proteins, the roles they play, and approaches for their inhibition in therapeutic situations of enzymes in both humans and bacteria that have heme groups. 

 

My research expertise

Mechanistic enzymology, Hemoproteins, Inhibitor design, Free radicals, Tuberculosis, Drug metabolism, Cytochrome P450, Conformational dynamics, Anticancer prodrugs

Degrees

PhD, Bioorganic Chemistry, Harvard University, 1968
MA, Chemistry, Harvard University, 1966
BS, Chemistry, Massachusetts Institute of Technology (MIT), 1964

Biography

Heme-containing proteins are critical for the function of essentially all life forms. In humans, they are involved in respiration, the synthesis of hormones and other vital molecules, the elimination of drugs, and various signaling pathways. My laboratory has investigated the structure, mechanism, biochemistry and role of heme proteins for many years. We have focused particularly on the human cytochrome P450, peroxidase, and heme oxygenase enzymes. Our contributions in this area include crystal structures of bacterial P450 enzymes and the human heme oxygenase, clarification of the mechanism of cytochrome P450 enzymes, the development of methods for the mechanism-based inactivation of P450 enzymes, and more recently studies of human cytochrome P450 enzymes that are selectively expressed in cancer cells and are potentially useful in the activation of anticancer drugs. We currently also work on two classes of heme proteins in Mycobacterium tuberculosis, the causative agent of tuberculosis: (a) the twenty cytochrome P450 enzymes, some of which potential targets for anti-tuberculosis drugs, and (b) the gas sensor that initiates the dormant, persistent stage of tuberculosis that is difficult to eradicate and which can be reactivated when the immune system is compromised.

The studies in my laboratory employ a diversity of techniques, including organic synthesis, molecular biology, enzymology, and multiple spectroscopic techniques. We frequently collaborate with laboratories that have complementary expertise in organic synthesis, X-ray crystallography, NMR, or resonance Raman spectroscopy.