Computer-based substrate specifity prediction for cytochrome P450

Application of molecular modeling for prediction of substrate specificity in cytochrome P450 1A2 mutants.

Molecular dynamics (MD) simulations of 7-ethoxy- and 7-methoxyresorufin bound in the active site of cytochrome P450 (P450) 1A2 wild-type and various mutants were used to predict changes in substrate specificity of the mutants. A total of 26 multiple mutants representing all possible combinations of five key amino acid residues, which are different between P450 1A1 and 1A2, were examined. The re...

Substrate inhibition kinetics for cytochrome P450-catalyzed reactions.

Most cytochrome P450 (P450 or CYP)-catalyzed reactions are adequately described by classical Michaelis-Menten kinetic parameters (e.g., Km and Vmax), which are usually determined by a saturation profile of velocity of product formation versus substrate concentration. In turn, these parameters may be used to predict pharmacokinetics. However, some P450 enzymes exhibit atypical or non-Michaelis-M...

The SMARTCyp cytochrome P450 metabolism prediction server

SUMMARY The SMARTCyp server is the first web application for site of metabolism prediction of cytochrome P450-mediated drug metabolism. AVAILABILITY The SMARTCyp server is freely available for use on the web at www.farma.ku.dk/smartcyp where the SMARTCyp Java program and source code is also available for download. CONTACT [email protected]; [email protected] SUPPLEMENTARY INFORMATION Supp...

CaSPredictor: a new computer-based tool for caspase substrate prediction

MOTIVATION In vitro studies have shown that the most remarkable catalytic features of caspases, a family of cysteineproteases, are their stringent specificity to Asp (D) in the S1 subsite and at least four amino acids to the left of scissile bound. However, there is little information about the substrate recognition patterns in vivo. The prediction and characterization of proteolytic cleavage s...

Cytochrome p450-based gene therapies for cancer.