Synthetic and Natural Compounds that Interact with Human Cytochrome P450 1A2 and Implications in Drug Development.

Authors: Wang B, Zhou SF
Human cytochrome P450 1A2 (CYP1A2) is one of the major CYPs in the liver ( approximately 13%) and metabolizes about 20% of clinically used drugs. CYP1A2 is a 515-residue protein with a molecular mass of 58,294 Dal. The recently published crystal structure of CYP1A2 in complex with alpha-naphthoflavone has showed a rather compact active site with a relatively small volume of the cavity of 375 A(3), which is 44.2% and 49.3% larger than that of CYP2A6 (260 A(3)) and CYP2E1 (190 A(3)), respectively. A series of residues in the substrate recognition regions of CYP1A2 (e.g. Arg108, Thr124, Thr223, Glu225, Phe226, Lys250, Arg251, Lys253, Asn312, Asp313, Glu318, Thr319, Asp320, Thr321, Val322, Leu382, Thr385, and Ile386) have been shown to play important roles in ligan…

Related posts:

1. Insights into the Structure, Function, and Regulation of Human Cytochrome P450 1A2.
2. Inhibition of procarcinogen-bioactivating human CYP1A1, CYP1A2 and CYP1B1 enzymes by melatonin
3. Malaria: therapeutic implications of melatonin
4. Association of disease-predisposition polymorphisms of the melatonin receptors and sunshine duration in the global human populations
5. The Consumption Of Melatonin, A Natural Hormone Segregated By The Own Human Body, Regulates Sleep Better Than Somniferous