Crystal structures of human cytochrome P450 3A4 bound to metyrapone and progesterone

Science

Volumn 305, Issue 5684, 2004, Pages 683-686

  Williams, Pamela A ^a   Cosme, Jose ^a   Matak Vinković, Dijana ^a   Ward, Alison ^a,c   Angove, Hayley C ^a   Day, Philip J ^a   Vonrhein, Clemens ^b   Tickle, Ian J ^a   Jhoti, Harren ^a  

^a ASTEX PHARMACEUTICALS   (United Kingdom)

^b GLOBAL PHASING LTD   (United Kingdom)

^c ASTRAZENECA   (United Kingdom)

Author keywords

[No Author keywords available]

Indexed keywords

CRYSTAL STRUCTURE; MEMBRANES; METABOLISM; OXIDATION;

DRUG MOLECULES; ISOFORMS; MICROSOMAL;

BIOCHEMISTRY;

CYTOCHROME P450 3A4; METYRAPONE; PROGESTERONE; CYP3A PROTEIN, HUMAN; CYP3A4 PROTEIN, HUMAN; CYTOCHROME P450; HEME; LIGAND; PHENYLALANINE; WATER;

BIOLOGY;

AEROBIC METABOLISM; ARTICLE; BACILLUS MEGATERIUM; CONFORMATIONAL TRANSITION; CRYSTAL STRUCTURE; DRUG PROTEIN BINDING; ENZYME ACTIVE SITE; PRIORITY JOURNAL; PROTEIN FOLDING; SACCHAROPOLYSPORA; SEQUENCE HOMOLOGY; STEREOCHEMISTRY; XENOBIOTIC METABOLISM; BINDING SITE; CHEMICAL STRUCTURE; CHEMISTRY; CRYSTALLIZATION; HUMAN; HYDROGEN BOND; HYDROPHOBICITY; METABOLISM; PROTEIN BINDING; PROTEIN CONFORMATION; PROTEIN SECONDARY STRUCTURE; PROTEIN TERTIARY STRUCTURE; X RAY CRYSTALLOGRAPHY;

BACILLUS MEGATERIUM; SACCHAROPOLYSPORA;

BINDING SITES; CRYSTALLIZATION; CRYSTALLOGRAPHY, X-RAY; CYTOCHROME P-450 ENZYME SYSTEM; HEME; HUMANS; HYDROGEN BONDING; HYDROPHOBICITY; LIGANDS; METYRAPONE; MODELS, MOLECULAR; PHENYLALANINE; PROGESTERONE; PROTEIN BINDING; PROTEIN CONFORMATION; PROTEIN STRUCTURE, SECONDARY; PROTEIN STRUCTURE, TERTIARY; WATER;

EID: 3442896773     PISSN: 00368075     EISSN: None     Source Type: Journal    
DOI: 10.1126/science.1099736     Document Type: Article

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37. We thank S. Rich, S. Maman, D. Cross, S. Kirton, and C. Murray for assistance with crystallization, characterization, and analysis; G. Williams for discussions; and F. W. Dahlquist for the provision of the pCWori+ expression vector. We acknowledge the European Synchrotron Radiation Facility for the provision of synchrotron radiation facilities and thank the industrial user group for assistance with data collection. Coordinates and structure factors of the ligand-free, metyrapone~, and progesterone-bound structures of CYP3A4 have been deposited in the Protein Data Bank (PDB) (entries 1W0E, 1W0F, and 1W0G).