ELECTRON-TRANSPORT IN CYTOCHROMES-P-450 BY COVALENT SWITCHING

被引:34
作者
BALDWIN, JE [1 ]
MORRIS, GM [1 ]
RICHARDS, WG [1 ]
机构
[1] OXFORD CTR MOLEC SCI, PHYS CHEM LAB, OXFORD OX1 3QZ, ENGLAND
关键词
D O I
10.1098/rspb.1991.0086
中图分类号
Q [生物科学];
学科分类号
07 ; 0710 ; 09 ;
摘要
The mechanism of electron transfer in cytochrome P-450cam is presented in terms of a covalent switching mechanism. We present a model of putidaredoxin built by homology, which helps explain protein-protein interactions. The mechanism is general enough to account for the genetic variations found in the superfamily of cytochromes P-450. The detail should assist in the design of novel P-450 inhibitors and may have wider implications. The sequence analysis supports our protein model, and highlights the role of cystein and aromatic residues in electron-transport mechanisms. Eukaryotic cytochromes P-450 appear to have evolved their own intramolecular tryptophan electron-transfer mediator, unlike prokaryotic P. putida P-450cam, which still relies upon the C-terminal tryptophan of its attendant electron-transport protein, putidaredoxin. On this basis our protein model is capable of rationalizing the transfer of electrons from NADH to the active site of P-450. At the electronic level the covalent switching that transfers pairs of electrons not only provides a plausible mechanism, but may also have ramifications in a wider context.
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页码:43 / 51
页数:9
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