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- W1976566451 abstract "A cytochrome P450 active site is buried within the protein molecule and several channels connect the catalytic cavity to the protein surface. Their role in P450 catalysis is still matter of debate. The aim of this study was to understand the possible relations existing between channels and substrate specificity.Time course studies were carried out with a collection of polycyclic substrates of increasing sizes assayed with a library of wild-type and chimeric CYP1A enzymes. This resulted in a matrix of activities sufficiently large to allow statistical analysis. Multivariate statistical tools were used to decipher the correlation between observed activity shifts and sequence segment swaps.The global kinetic behavior of CYP1A enzymes toward polycyclic substrates is significantly different depending on the size of the substrate. Mutations which are close or lining the P450 channels significantly affect this discrimination, whereas mutations distant from the P450 channels do not.Size discrimination is taking place for polycyclic substrates at the entrance of the different P450 access channels. It is thus hypothesized that channels differentiate small from large substrates in CYP1A enzymes, implying that residues located at the surface of the protein may be implied in this differential recognition.Catalysis thus occurs after a two-step recognition process, one at the surface of the protein and the second within the catalytic cavity in enzymes with a buried active site." @default.
- W1976566451 created "2016-06-24" @default.
- W1976566451 creator A5044887967 @default.
- W1976566451 creator A5062503534 @default.
- W1976566451 creator A5082930636 @default.
- W1976566451 date "2015-04-01" @default.
- W1976566451 modified "2023-10-05" @default.
- W1976566451 title "Access channels to the buried active site control substrate specificity in CYP1A P450 enzymes" @default.
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- W1976566451 doi "https://doi.org/10.1016/j.bbagen.2014.12.015" @default.
- W1976566451 hasPubMedId "https://pubmed.ncbi.nlm.nih.gov/25529298" @default.
- W1976566451 hasPublicationYear "2015" @default.
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