On the membrane topology of vertebrate cytochrome P-450 proteins

David Nelson, H. W. Strobel

Research output: Contribution to journalArticle

314 Citations (Scopus)

Abstract

Hydropathy profiles of 34 aligned cytochrome P-450 sequences were compared to identify potential transmembrane segments. Eleven regions with the potential to cross a membrane in at least some P-450 sequences were detected. The known sidedness of several residues and peptides was used to eliminate some of these regions from consideration. Further arguments based on the location and orientation of the heme relative to the membrane excluded others. This process of elimination was continued until only two regions remained. These two segments, present in the first 66 amino acids of the P-450 NH2 termini, are proposed as the only transmembrane peptides of vertebrate microsomal P-450s. Mitochondrial P-450s may have a different membrane association. The three-dimensional structure of cytochrome P-450(cam) was examined for the location of conserved charged residues. These residues occurred mainly on the opposite surface from the substrate-binding site and along the edges of the flat triangular P-450(cam). A model is proposed for vertebrate microsomal P-450s that is similar to P-450(cam). The substrate-binding site faces the membrane, the heme is parallel to the membrane surface, and two NH2-terminal transmembrane segments anchor the protein to the bilayer.

Original languageEnglish (US)
Pages (from-to)6038-6050
Number of pages13
JournalJournal of Biological Chemistry
Volume263
Issue number13
StatePublished - 1988
Externally publishedYes

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Cytochrome P-450 Enzyme System
Vertebrates
Topology
Membranes
Cams
Proteins
Heme
Camphor 5-Monooxygenase
Binding Sites
Peptides
Substrates
Anchors
Membrane Potentials
Amino Acids

All Science Journal Classification (ASJC) codes

  • Biochemistry

Cite this

On the membrane topology of vertebrate cytochrome P-450 proteins. / Nelson, David; Strobel, H. W.

In: Journal of Biological Chemistry, Vol. 263, No. 13, 1988, p. 6038-6050.

Research output: Contribution to journalArticle

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