Research Topics
| I A PikulevaSummaryAffiliation: University of Texas Medical Branch Country: USA Publications
Research Grants
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Detail Information
Publications
Cytochrome P450s and cholesterol homeostasisIrina A Pikuleva
Department of Pharmacology and Toxicology, University of Texas Medical Branch, 301 University Boulevard, Galveston, TX 77555 1031, USA
Pharmacol Ther 112:761-73. 2006..Finally, one of the major drug-metabolizing P450s CYP3A4 seems to contribute to bile acid biosynthesis as well. The 9 P450s will be the focus of this review and assessed as drug targets for cholesterol lowering...
Studies of membrane topology of mitochondrial cholesterol hydroxylases CYPs 27A1 and 11A1Irina A Pikuleva
Department of Ophthalmology and Visual Sciences, Case Western Reserve University and University Hospitals Case Medical Center, Cleveland, OH 44106, USA
Lipids 43:1127-32. 2008..This data is consistent with those obtained previously by us and others and provide new information about the membrane topology of CYPs 27A1 and 11A1...- Novel sterols synthesized via the CYP27A1 metabolic pathwayIrina Pikuleva
Department of Pharmacology and Toxicology, University of Texas Medical Branch, 301 University Blvd, Galveston, TX 77555 103, USA
Arch Biochem Biophys 420:35-9. 2003.... - Cholesterol-metabolizing cytochromes P450Irina A Pikuleva
Department of Pharmacology and Toxicology, University of Texas, Medical Branch, 301 University Blvd, Galveston, TX 77555 1031, USA
Drug Metab Dispos 34:513-20. 2006..Studies of cholesterol-metabolizing P450s suggest that their activities could be modulated post-translationally and that they should also be considered as targets for regulation of cholesterol homeostasis... - Putative helix F contributes to regioselectivity of hydroxylation in mitochondrial cytochrome P450 27A1I A Pikuleva
Department of Pharmacology and Toxicology, University of Texas Medical Branch, Galveston, Texas 77555 1031, USA
Biochemistry 40:7621-9. 2001..We propose that putative helices F and G form the sides of the substrate-access channel, thus providing the additional mechanism to control regioselectivity of hydroxylation in mitochondrial P450s... - The tertiary structure of full-length bovine adrenodoxin suggests functional dimersI A Pikuleva
Department of Biochemistry, Vanderbilt University School of Medicine, Nashville, Tennessee, 37232 0146, USA
Arch Biochem Biophys 373:44-55. 2000..From these results it can be considered that the mechanism of electron transfer is not necessarily the same in different mitochondrial P450 systems... - Membrane binding and substrate access merge in cytochrome P450 7A1, a key enzyme in degradation of cholesterolK Nakayama
Department of Pharmacology and Toxicology, University of Texas Medical Branch, Galveston, Texas 77555-1031, USA
J Biol Chem 276:31459-65. 2001..The results provide an understanding of both the P450 7A1-membrane interactions and the mechanism for substrate specificity... - An additional electrostatic interaction between adrenodoxin and P450c27 (CYP27A1) results in tighter binding than between adrenodoxin and p450scc (CYP11A1)I A Pikuleva
Department of Biochemistry, Vanderbilt University School of Medicine, Nashville, Tennessee 37232 0146, USA
J Biol Chem 274:2045-52. 1999.... - A simple and rapid method to measure cholesterol binding to P450s and other proteinsNatalia Mast
Department of Pharmacology and Toxicology, University of Texas Medical Branch, Galveston TX 77555-1031, USA
J Lipid Res 46:1561-8. 2005..These membranes were also found to hold proteins through hydrophobic interactions. Thus, the cholesterol binding properties of a wide variety of proteins could be characterized using this filter assay... - Cholesterol-metabolizing cytochromes P450: implications for cholesterol loweringIrina A Pikuleva
Case Western Reserve University, University Hospitals Case Medical Center, Department of Ophthalmology and Visual Sciences, Cleveland, OH 44106, USA
Expert Opin Drug Metab Toxicol 4:1403-14. 2008..This review summarizes new information about cytochrome P450 enzymes 7A1, 27A1 and 46A1. These enzymes play key roles in cholesterol elimination and have the potential to serve as targets for cholesterol-lowering... - Use of complementary cation and anion heavy-atom salt derivatives to solve the structure of cytochrome P450 46A1Mark Andrew White
Sealy Center for Structural and Molecular Biophysics, UTMB Galveston, TX 77555, USA
Acta Crystallogr D Biol Crystallogr 64:487-95. 2008..The use of complementary cation and anion heavy-atom salt derivatives is a convenient and powerful tool for MIR(AS) structure solution... - Combined use of mass spectrometry and heterologous expression for identification of membrane-interacting peptides in cytochrome P450 46A1 and NADPH-cytochrome P450 oxidoreductaseNatalia Mast
Department of Ophthalmology and Visual Sciences, Case Western Reserve University, Cleveland, OH 44106, USA
Arch Biochem Biophys 483:81-9. 2009..This information may provide insight in the deleterious nature of these mutations... - Membrane-protein interactions contribute to efficient 27-hydroxylation of cholesterol by mitochondrial cytochrome P450 27A1Dilyara Murtazina
Department of Pharmacology and Toxicology and Sealy Center for Structural Biology, University of Texas Medical Branch, Galveston, Texas 77555, USA
J Biol Chem 277:37582-9. 2002..The results provide insight into the membrane topology of mitochondrial P450s and indicate the importance of membrane-protein interactions in the efficiency of reactions catalyzed by P450 27A1... - Structural basis of drug binding to CYP46A1, an enzyme that controls cholesterol turnover in the brainNatalia Mast
Department of Ophthalmology and Visual Sciences, Case Western Reserve University, Cleveland, Ohio 44106, USA
J Biol Chem 285:31783-95. 2010..Co-complexes with tranylcypromine, thioperamide, and voriconazole represent the first structural characterization of the drug binding to a P450 enzyme... - Crystal structures of substrate-bound and substrate-free cytochrome P450 46A1, the principal cholesterol hydroxylase in the brainNatalia Mast
Department of Pharmacology and Toxicology, The Sealy Center for Structural Biology and Molecular Biophysics, University of Texas Medical Branch, Galveston, TX 77555, USA
Proc Natl Acad Sci U S A 105:9546-51. 2008..Structural and biochemical data provide evidence that CYP46A1 activity could be altered by exposure to some therapeutic drugs and potentially other xenobiotics... - Distinct binding of cholesterol and 5beta-cholestane-3alpha,7alpha,12alpha-triol to cytochrome P450 27A1: evidence from modeling and site-directed mutagenesis studiesNatalia Mast
Department of Pharmacology and Toxicology, University of Texas Medical Branch, Galveston, Texas 77555 1031, USA
Biochemistry 45:4396-404. 2006..Distinct binding of the CYP27A1 substrates may provide insight into why phenotypic manifestations of cerebrotendinous xanthomatosis, a disease associated with CYP27A1 deficiency, are so diverse... - Cholesterol binding to cytochrome P450 7A1, a key enzyme in bile acid biosynthesisNatalia Mast
Department of Pharmacology and Toxicology, University of Texas Medical Branch, Galveston, Texas 77555 1031, USA
Biochemistry 44:3259-71. 2005..Our data indicate that a tight fit of cholesterol in the enzyme active site is in part responsible for the high efficiency of cholesterol turnover by CYP7A1... - Active-site topology of bovine cholesterol side-chain cleavage cytochrome P450 (P450scc) and evidence for interaction of tyrosine 94 with the side chain of cholesterolI A Pikuleva
Department of Biochemistry, Vanderbilt University, School of Medicine, Nashville, Tennessee 37232 0146, USA
Arch Biochem Biophys 322:189-97. 1995.... - Putative F-G loop is involved in association with the membrane in P450scc (P450 11A1)Irina A Pikuleva
Department of Pharmacology and Toxicology, University of Texas Medical Branch, Galveston, TX 77555-1031, USA
Mol Cell Endocrinol 215:161-4. 2004..These data indicate that the putative F-G loop is the site of attachment to the membrane in P450 11A1 and changes in the enzyme-membrane interactions may affect the rate of catalysis... - Broad substrate specificity of human cytochrome P450 46A1 which initiates cholesterol degradation in the brainNatalia Mast
Department of Pharmacology and Toxicology, University of Texas Medical Branch, Galveston, Texas 77555 1031, USA
Biochemistry 42:14284-92. 2003.... - Phospholipids modify substrate binding and enzyme activity of human cytochrome P450 27A1Dilyara A Murtazina
Department of Pharmacology and Toxicology, University of Texas Medical Branch, Galveston, TX 77555-1031, USA
J Lipid Res 45:2345-53. 2004..Our study shows the potential for PLs to regulate the activity of P450 27A1 in vivo and alter the amount of cholesterol degraded through the "classical" and "alternative" bile acid biosynthetic pathways... - Expression of human cytochrome P450 46A1 in Escherichia coli: effects of N- and C-terminal modificationsNatalia Mast
Department of Pharmacology and Toxicology, University of Texas Medical Branch, Galveston, TX 77555-1031, USA
Arch Biochem Biophys 428:99-108. 2004..3-0.8% of high molecular weight aggregates and their catalytic efficiencies are decreased no more than 2.3-fold...
Research Grants
- Cholesterol-metabolizing P450s and Alzheimer's diseaseIrina Pikuleva; Fiscal Year: 2007..If funded, the release time and salary support will significantly enhance the P.I.'s career in basic science research and make it more medically oriented. ..
- Significance of CYP46A1 and other P450s in retinal functionIrina Pikuleva; Fiscal Year: 2007..Relevance (for lay audience). This research will be critical for understanding the development of certain eye diseases that reduce vision. ..