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Paul Ortiz De Montellano, PhD

Title(s)Professor, Pharmaceutical Chemistry
SchoolSchool of Pharmacy
Phone415-476-2903
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    Collapse Biography 
    Collapse Education and Training
    Massachusetts Institute of TechnologyB.S.1964Chemistry
    Harvard UniversityM.A., Ph.D.1968Chemistry
    Eidgenossische Technische Hochschule, ZurichPostdoc1969Chemistry

    Collapse Overview 
    Collapse Overview
    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.

    Collapse Research 
    Collapse Research Activities and Funding
    Oxygen Sensors and P450 Monooxygenases in Mycobacertium tuberculosis
    NIH/NIAID R01AI074824Sep 1, 2007 - Aug 31, 2017
    Role: Principal Investigator
    2000 GORDON CONFERENCE ON TETRAPYRROLES
    NIH/NIDDK R13DK058032Jul 1, 2000 - Jun 30, 2001
    Role: Principal Investigator
    Structure Biology and Targeted Drug Design for AIDS
    NIH/NIGMS P01GM056531Sep 1, 1997 - Aug 31, 2007
    Role: Principal Investigator
    STRUCTURAL BIOLOGY AND TARGETED DRUG DESIGN FOR AIDS
    NIH/NIGMS P01GM039552Sep 1, 1987 - Aug 31, 1997
    Role: Co-Investigator
    LIVER CORE CENTER
    NIH P30AM026743Jul 1, 1985 - Jun 30, 1990
    Role: Co-Investigator
    BIOCHEMISTRY AND HEPATIC TOXICITY OF CARBON RADICALS
    NIH/NIGMS R01GM032488Jul 1, 1983 - Jun 30, 2009
    Role: Principal Investigator
    Bio-Organic Biomedical Mass Spectrometry Resource
    NIH P41RR001614Mar 1, 1982 - May 31, 2015
    Role: Co-Investigator
    Hemoprotein Oxidation and Heme Catabolism
    NIH/NIDDK R01DK030297Jan 1, 1982 - Jun 30, 2014
    Role: Principal Investigator
    HEMOLYTIC ANEMIA AND ABNORMAL HEME CATABOLITES
    NIH/NIADDK R01AM030297Jan 1, 1982 - Dec 31, 1989
    Role: Principal Investigator
    Mechanism, Specificity, and Inhibition of Cytochrome P450
    NIH/NIGMS R01GM025515Jul 1, 1978 - Jun 30, 2015
    Role: Principal Investigator
    SELECTIVE DESTRUCTION OF CYTOCHROME P450 BY DRUGS
    NIH/NIGMS R37GM025515Jul 1, 1978 - Jun 30, 1999
    Role: Principal Investigator
    Resource for Biocomputing, Visualization, and Informatics
    NIH/NCRR P41RR001081Jun 1, 1976 - Sep 14, 2012
    Role: Co-Investigator

    Collapse ORNG Applications 
    Collapse Global Health

    Collapse Bibliographic 
    Collapse Publications
    Publications listed below are automatically derived from MEDLINE/PubMed and other sources, which might result in incorrect or missing publications. Researchers can login to make corrections and additions, or contact us for help.
    List All   |   Timeline
    1. Ortiz de Montellano PR. Potential drug targets in the Mycobacterium tuberculosis cytochrome P450 system. J Inorg Biochem. 2018 03; 180:235-245. PMID: 29352597.
      View in: PubMed
    2. Ortiz de Montellano PR. Heme and I. J Biol Chem. 2015 Sep 04; 290(36):21833-44. PMID: 26195628; PMCID: PMC4571939.
    3. Ortiz de Montellano PR. Cytochrome P450-activated prodrugs. Future Med Chem. 2013 Feb; 5(2):213-28. PMID: 23360144; PMCID: PMC3697796.
    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. PMID: 18642140.
      View in: 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. PMID: 12195813.
      View in: PubMed
    6. Montellano PR. The mechanism of heme oxygenase. Curr Opin Chem Biol. 2000 Apr; 4(2):221-7. PMID: 10742194.
      View in: 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. PMID: 9860925.
      View in: PubMed