University of California San Francisco
Helen Diller Family Comprehensive Cancer Center
Paul R. Ortiz de Montellano, PhD

Paul R. Ortiz de Montellano, PhD

Professor, Departments of Pharmaceutical Chemistry and Pharmacology, UCSF

Cancer Center Program Memberships

Affiliate Member

Research Summary

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.

Education

Mass. Institute of Technology (Cambridge, MA), B.S., 1964, Chemistry
Harvard University (Cambridge, MA), M.A., 1966, Chemistry
Harvard University (Cambridge, MA), Ph.D., 1968, Bioorganic Chemistry
Eidg. Tech. Hochschule (Zurich, Switzerland), Postdoc, 1968-1969, Bioorganic Chemistry


Professional Experience

  • 1969-1971
    Group Leader, Syntex Research Laboratories
  • 1972-1980
    Assistant/Associate Professor, University of California, San Francisco
  • 1980-present
    Professor of Chemistry, Pharmaceutical Chemistry, and Pharmacology, University of California, San Francisco
  • 1982-1994
    Vice Chairman, Department of Pharmaceutical Chemistry
  • 1978-1979
    Professeur Associe, Institut de Chimie, Universite Louis Pasteur, Strasbourg, France
  • 1985-1986
    Honorary Fellow, Department of Biochemistry, University College, London
  • 1993-1994
    Professeur Rhone Poulenc, Universite René Descartes (Paris V), Paris, France
  • 2000-2001
    Visiting Academic, Department of Biochemistry & Molec. Biol., University College, London

Honors & Awards

  • 1960-1964
    McDermott Scholar (MIT)
  • 1965-1968
    NIH Predoctoral Fellow (Harvard)
  • 1968-1969
    NATO Postdoctoral Fellow
  • 1988
    Alfred P. Sloan Foundation Research Science
  • 1989
    John Moffat Lecturer, University of British Columbia
  • 1989-1999
    NIH MERIT Award
  • 1989, 1996, 1997
    UCSF Long Foundation Award for Excellence in Teaching
  • 1991
    King/Chavez/Parks Visiting Professor, University of Michigan
  • 1991
    Distinguished University Lecturer, University of Utah
  • 1994
    Wellcome Visiting Professor, Washington State University
  • 1994
    B. B. Brodie Award in Drug Metabolism of the American Society of Pharmacology and Experimental Therapeutics
  • 1998
    Robert A. Welch Foundation Lecturer, University of Texas Campuses
  • 2000
    Chauncey Leake Lecturer, University of Texas Medical Branch Galveston
  • 2001
    Karcher Lecturer, University of Oklahoma

Selected Publications

  1. Ortiz de Montellano PR. Potential drug targets in the Mycobacterium tuberculosis cytochrome P450 system. J Inorg Biochem. 2018 Mar; 180:235-245.
    View on PubMed
  2. Ortiz de Montellano PR. Heme and I. J Biol Chem. 2015 Sep 04; 290(36):21833-44.
    View on PubMed
  3. Ortiz de Montellano PR. Cytochrome P450-activated prodrugs. Future Med Chem. 2013 Feb; 5(2):213-28.
    View on PubMed
  4. Ortiz de Montellano PR. Mechanism and role of covalent heme binding in the CYP4 family of P450 enzymes and the mammalian peroxidases. Drug Metab Rev. 2008; 40(3):405-26.
    View on PubMed
  5. Ortiz de Montellano PR, De Voss JJ. Oxidizing species in the mechanism of cytochrome P450. Nat Prod Rep. 2002 Aug; 19(4):477-93.
    View on PubMed
  6. Montellano PR. The mechanism of heme oxygenase. Curr Opin Chem Biol. 2000 Apr; 4(2):221-7.
    View on PubMed
  7. Ortiz de Montellano PR, Nishida C, Rodriguez-Crespo I, Gerber N. Nitric oxide synthase structure and electron transfer. Drug Metab Dispos. 1998 Dec; 26(12):1185-9.
    View on PubMed

Go to UCSF Profiles, powered by CTSI