Flexibility and stability of the structure of cytochromes P450 3A4 and BM-3
Language English Country England, Great Britain Media print
Document type Journal Article, Research Support, Non-U.S. Gov't
PubMed
10806389
DOI
10.1046/j.1432-1327.2000.01305.x
PII: ejb1305
Knihovny.cz E-resources
- MeSH
- Bacterial Proteins * MeSH
- Cytochrome P-450 CYP3A MeSH
- Escherichia coli enzymology MeSH
- Heme chemistry MeSH
- Protein Conformation MeSH
- NADPH-Ferrihemoprotein Reductase MeSH
- Pliability MeSH
- Carbon Monoxide chemistry MeSH
- Mixed Function Oxygenases chemistry MeSH
- Plasmids MeSH
- Spectrophotometry MeSH
- Enzyme Stability MeSH
- Cytochrome P-450 Enzyme System chemistry MeSH
- Temperature MeSH
- Pressure MeSH
- Troleandomycin chemistry MeSH
- Protein Binding MeSH
- Binding Sites MeSH
- Publication type
- Journal Article MeSH
- Research Support, Non-U.S. Gov't MeSH
- Names of Substances
- Bacterial Proteins * MeSH
- CYP3A protein, human MeSH Browser
- CYP3A4 protein, human MeSH Browser
- Cytochrome P-450 CYP3A MeSH
- flavocytochrome P450 BM3 monoxygenases MeSH Browser
- Heme MeSH
- NADPH-Ferrihemoprotein Reductase MeSH
- Carbon Monoxide MeSH
- Mixed Function Oxygenases MeSH
- Cytochrome P-450 Enzyme System MeSH
- Troleandomycin MeSH
The flexibility of the structure and compressibility of the respective active site of cytochromes P450 3A4 (CYP3A4) and BM-3 (CYP102) were studied using absorption spectroscopy in the ultraviolet and visual regions. Conformational changes in the overall protein structures of both CYP3A4 and CYP102 due to the effects of temperature and pressure are reversible. However, the enzymes differ in the properties of their active sites. The CYP3A4 enzyme denatures to the inactive P420 form relatively easy, at 3000 bar over half is converted to P420. The compressibility of its active site is lower than that of CYP102 and is greater with the substrate bound, which is in line with the observed lack of a stabilizing effect of the substrate on its conformation under pressure. In contrast, CYP102, although having the most compressible active site among the P450s, possesses a structure that does not denature easily to the inactive (P420) form under pressure. In this respect, it resembles the P450 isolated from acidothermophilic archaebacteria [McLean, M.A., Maves, S.A., Weiss, K.E., Krepich, S. & Sligar, S.G. (1998) Biochem. Biophys. Res. Commun. 252, 166-172].
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