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Protein-Protein Interactions in the P450 Monooxygenase System

  • John B. Schenkman
  • Ingela Jansson
  • Gary Davis
  • Paul P. Tamburini
  • Zhongqing Lu
  • Zhe Zhang
  • James F. Rusling
Part of the NATO ASI Series book series (NSSA, volume 303)

Abstract

Cytochrome bs is a small acidic hemoprotein that functions as an electron transfer protein. It is a ubiquitous mammalian membrane protein, found in the endoplasmic reticulum of most tissues. Its primary structure is highly conserved with sequence identities of greater than 89% in mammals and greater than 71% between rat and chicken (Figure I). Even in comparisons between plant (rice and tobacco) cytochrome bs with that of mammals sequence identity is greater than 35%. Twenty-five of the one hundred and thirtythree amino acids of rabbit cytochrome bs are acidic residues, glutamate or aspartate. Cytochrome bs has a number of its very highly conserved acidic residues around an exposed heme edge (Figure 2), some of which are delineated in Figure I (bold type). Residues around the exposed heme and the heme are shown in ball and stick model. It was shown quite early that cytochrome bs uses its acidic residues for stabilization of interactions with its electron transfer (redox) partners. Although not its normal redox partner, cytochrome c has been used to study electron transfer with cytochrome b5, and, since the crystal structure of both proteins have been elucidated,I-3 surface maps of the topologies of cytochrome bs and cytochrome c were constructed and fitted together making use of the invariant anionic and cationic charges respectively, ringing the exposed heme prosthetic groups as a means for determining the docking domains of the two proteins. 3 Interaction models between cytochrome b5 and methemoglobin have likewise been constructed which make use of charge pairings. 4 Interaction between erythrocyte cytochrome bs and its reductase was greatly inhibited by increased ionic strength,S which suggested that such interaction also utilizes complementary charge pairing for efficient electron transfer.

Keywords

P450 Reductase Redox Partner Ionic Activity Coefficient Heme Prosthetic Group Carboxyl Residue 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.

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Copyright information

© Springer Science+Business Media New York 1999

Authors and Affiliations

  • John B. Schenkman
    • 1
  • Ingela Jansson
    • 1
  • Gary Davis
    • 2
  • Paul P. Tamburini
    • 2
  • Zhongqing Lu
    • 3
  • Zhe Zhang
    • 3
  • James F. Rusling
    • 3
  1. 1.Department of PharmacologyUniversity of Connecticut Health CenterFarmingtonUSA
  2. 2.Bayer CorporationPharmaceutical DivisionWest HavenUSA
  3. 3.Department of ChemistryUniversity of ConnecticutStorrsUSA

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