Crystal of a cytochrome-ligand complex and methods of use

Details Crystal of a cytochrome-ligand complex and methods of use Crystal of a cytochrome-ligand complex and methods of use

2011-05-27

2011-12-13

Noakes, Suzanne M (Department: 1656)

Chemistry: natural resins or derivatives; peptides or proteins;

Proteins, i.e., more than 100 amino acid residues

C702S019000, C702S027000, C703S011000, C435S007710

Reexamination Certificate

active

08076457

ABSTRACT:
The teachings relates to the three-dimensional structure of a crystal of a cytochrome protein complexed with a ligand. The three-dimensional structure of four cytochrome P450 2A6-ligand complexes are disclosed. Cytochrome P450 2A6-ligand crystal structures, wherein the ligand is an inhibitor molecule, are useful for providing structural information that may be integrated into drug screening and drug design processes. Thus, the teachings also relate to methods for utilizing a crystal structure of a cytochrome P450 2A6-ligand complex for identifying, designing, selecting, or testing inhibitors of the cytochrome protein. Such inhibitors are useful as therapeutics for the treatment or modulation of i) diseases; ii) disease symptoms; or iii) the effect of other physiological events mediated by the cytochrome.

REFERENCES:
patent: 2004/0106216 (2004-06-01), Matsui
patent: 2004/0137518 (2004-07-01), Lambert
Lewis et al. (Molecular modeling of the human cytochrome P450 isoform CYP2A6 and investigations of CYP2A substrate selectivity, Toxicology, 133, (1999), pp. 1-33).
Branden et al., “Introduction to Protein Structure Second Edition”, Garland Publishing Inc., New York, 1999.
Drenth et al., “Principles of X-ray Crystallography,” Springer, New York, 1995.
Giege et al., “Crystallogenesis of Biological Macromolecules: Facts and Perspectives,” Acta Cryst., 1994, D50: 339-350.
Kierzek et al., Biophys Chem, 2001, 91:1-20.
Koenigs et al., “Mechanism-based inactivation of P450 2A6 by furanocoumarins,” Biochemistry, 1998, 37, 10047-10061.
Lewis et al., “Molecular modeling of the human cytochrome P450 isoform CYP2A6 and investigations of CYP2A substrate selectivity,” Toxicology, 133, (1999), pp. 1-33.
Poso, Antti et al., “A comparative molecular field analysis of cytochrome P450 2A5 and 2A6 inhibitors,” Journal of Computer-Aided Molecular Design (2001), 15 (3), 195-202.
Sellers, Edward et al., “Inhibition of cytochrome P450 2A6 increases nicotine's oral bioavailability and decreases smoking,” Clinical Pharmacology & Therapeutics, pp. 35-43, Jul. 2000.
Turpeinen, Miia et al., “Selective inhibition of CYP2B6-catalyzed bupropion hydroxylation in human liver microsomes in vitro,” Drug Metabolism and Disposition (2004), 32(6), 626-631.
Wiencek, Ann Rev Biomed Eng, 1999, 1:505-534.
Williams et al., “Crystal structure of human cytochrome P450 2C9 with bound warfarin,” Nature, 2003, 424 (6947) pp. 464-468, Epub Jul. 13, 2003.
Yano, Jason K. et al., “Structures of human microsomal cytochrome P450 2A6 complexed with coumarin and methoxsalen,” Nature Structural & Molecular Biology (2005), 12(9), 822-823.
Zhang, Wenjiang et al., “Evaluation of methoxsalen, tranylcypromine, and tryptamine as specific and selective CYP2A6 inhibitors in vitro,” Drug Metabolism and Disposition (2001), 9(6), 897-902.

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