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Catalytic Site Atlas

CSA LITERATURE entry for 1bu7

E.C. nameunspecific monooxygenase
SpeciesBacillus megaterium ()
E.C. Number (IntEnz) 1.14.14.1
CSA Homologues of 1bu7
CSA Entries With UniProtID P14779
CSA Entries With EC Number 1.14.14.1
PDBe Entry 1bu7
PDBSum Entry 1bu7
MACiE Entry 1bu7

Literature Report

IntroductionCytochromes P450, a gene superfamily of heme proteins found in all eukaryotes, most prokaryotes, and Archaea, catalyze the monooxygenation of a wide variety of organic molecules. P450 reactions of biological significance include steroid biogenesis, drug metabolism, procarcinogen activation, xenobiotic detoxification, and fatty acid metabolism.
MechansimElectron transfer from a redox partner to the P450 is a key step in the P450 catalytic cycle. The redox partner for P450BM-3 is a covalently bound FAD/FMN-dependent NADPH-cytochrome P450 oxidoreductase (CPR). In CPR, FAD serves as an electron acceptor from NADPH, passes them to FMN which interacts with and reduces the P450BM-3 haem group.
Binding of the substrate promotes electron transfer to P450 haem, reducing the iron from Fe(III) to Fe(II). Dioxygen binds and thus Fe(II) is oxidised back to Fe(III). A second electron is passed to the haem forming a superoxide species rapidly followed by proton donation by catalytic water. A second proton is delivered causing either non productive peroxide formation or loss of water and the formation of the low spin Fe(IV) oxo complex.
The rebound mechanism forms the alcohol group on the substrate. The Fe(IV)-oxo complex undergoes spin inversion to form a radical oxo group which removes a hydrogen from the substrate to form a radical carbon centre and an alcohol group on Fe(IV). The new radical then attacks the oxygen to form the alcohol group and Fe(III), completing the catalytic cycle.
Reaction

Catalytic Sites for 1bu7

Annotated By Reference To The Literature - Site 3 (Perform Site Search)
ResidueChainNumberUniProtKB NumberFunctional PartFunctionTargetDescription
ThrA268269macie:sideChainRequired for a robust framework that positions water appropriately during the reaction to prevent peroxide formation.
CysA400401macie:sideChainActs to increase the redox potential of the haem iron with the aid of residue 383.
PheA393394macie:sideChainActs to increase the redox potential of the haem iron by increasing the electron density around cys400.

Annotated By Reference To The Literature - Site 4 (Perform Site Search)
ResidueChainNumberUniProtKB NumberFunctional PartFunctionTargetDescription
ThrB268269macie:sideChainRequired for a robust framework that positions water appropriately during the reaction to prevent peroxide formation.
CysB400401macie:sideChainActs to increase the redox potential of the haem iron with the aid of residue 383.
PheB393394macie:sideChainActs to increase the redox potential of the haem iron by increasing the electron density around cys400.

Literature References

Notes:HOH23 is theorised to be displaced during the reaction from its crystalographic position during substrate binding, allowing O2 binding. The substrate is theorised to move closer to the haem during the reaction cycle to allow the reaction.
Sevrioukova IF
Structure of a cytochrome P450-redox partner electron-transfer complex.
Proc Natl Acad Sci U S A 1999 96 1863-1868
PubMed: 10051560
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