Paul Ortiz De Montellano, PhD
Professor
Pharmaceutical Chemistry
School of Pharmacy
paul.ortiz.de.montellano@ucsf.edu 415-476-2903
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.
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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.
Awards
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- RT Williams Distinguished Scientific Achievement Award, International Society for the Study of Xenob, 2007
- Dean’s Recognition for Excellence in Teaching, UCSF School of Pharmacy, 2006-2013
- Volwiler Research Achievement Award, American Association of Colleges of Pharmacy, 2006
- Ingelheim Boehringer Lecture Award, Division of Chemical Toxicology, 226th American Chemical Society, 2003
- Bernard B. Brodie Award in Drug Metabolism, American Society for Pharmacology and Experimental Thera, 1994
- Rhône-Poulenc Professor, Université René Descartes, Paris, France, 1993-1994
- 125 Most Outstanding People, UCSF, 1990
- MERIT Grant Award, National Institutes of Health, 1989-1999
- Elected Fellow, American Association for the Advancement of Scie, 1988
- Joseph M. Long Foundation Prize for Excellence in Teaching, UCSF School of Pharmacy, 1985
- Alfred P. Sloan Research Fellow, 1978-1992
- NATO Postdoctoral Fellow, ETH Switzerland, 1968-1969
- NIH Graduate Fellowship, Harvard University, 1966-1968
Education & Training
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- Postdoc Chemistry Eidgenossische Technische Hochschule, Zurich 1969
- M.A., Ph.D. Chemistry Harvard University 1968
- B.S. Chemistry Massachusetts Institute of Technology 1964
Grants and Projects
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- Oxygen Sensors and P450 Monooxygenases in Mycobacertium tuberculosis, NIH, 2007-2019
- Mechanism, Specificity, and Inhibition of Cytochrome P450, NIH, 1978-2016
- Bio-Organic Biomedical Mass Spectrometry Resource, NIH, 1982-2015
- Hemoprotein Oxidation and Heme Catabolism, NIH, 1982-2014
- Resource for Biocomputing, Visualization, and Informatics, NIH/NCRR, 1976-2012
- Biochemistry and Hepatic Toxicity of Carbon Radicals, NIH, 1983-2009
- Structure Biology and Targeted Drug Design for AIDS, NIH, 1997-2007
- 2000 Gordon Conference on Tetrapyrroles, NIH, 2000-2001
- Selective Destruction of Cytochrome P450 by Drugs, NIH, 1978-1999
- Structural Biology and Targeted Drug Design for Aids, NIH, 1987-1997
- LIVER CORE CENTER, NIH, 1985-1990
- Hemolytic Anemia and Abnormal Heme Catabolites, NIH, 1982-1989
Publications (6)
Top publication keywords:
Mycobacterium tuberculosisHemeDrug Delivery SystemsNitric Oxide SynthaseAzolesProdrugsCytochrome P-450 Enzyme InhibitorsHeme Oxygenase (Decyclizing)Cytochrome P-450 Enzyme SystemHydroxylationElectron TransportAntitubercular AgentsFatty AcidsMycobacterium smegmatisPeroxidases
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Potential drug targets in the Mycobacterium tuberculosis cytochrome P450 system.
Journal of inorganic biochemistry 2018 Ortiz de Montellano PR -
Heme and I.
The Journal of biological chemistry 2015 Ortiz de Montellano PR -
Cytochrome P450-activated prodrugs.
Future medicinal chemistry 2013 Ortiz de Montellano PR -
Mechanism and role of covalent heme binding in the CYP4 family of P450 enzymes and the mammalian peroxidases.
Drug metabolism reviews 2008 Ortiz de Montellano PR -
The mechanism of heme oxygenase.
Current opinion in chemical biology 2000 Montellano PR -
Nitric oxide synthase structure and electron transfer.
Drug metabolism and disposition: the biological fate of chemicals 1998 Ortiz de Montellano PR, Nishida C, Rodriguez-Crespo I, Gerber N