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Protein-Protein Interactions in the P450 Monooxygenase System

  • Chapter
Molecular and Applied Aspects of Oxidative Drug Metabolizing Enzymes

Part of the book series: NATO ASI Series ((NSSA,volume 303))

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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.

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Authors and Affiliations

  1. Department of Pharmacology, University of Connecticut Health Center, MC-1505, Farmington, Connecticut, 06030, USA

    John B. Schenkman & Ingela Jansson

  2. Bayer Corporation, Pharmaceutical Division, West Haven, Connecticut, 06516, USA

    Gary Davis & Paul P. Tamburini

  3. Department of Chemistry, University of Connecticut, Storrs, Connecticut, 06269, USA

    Zhongqing Lu, Zhe Zhang & James F. Rusling

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  1. John B. Schenkman
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  2. Ingela Jansson
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  4. Paul P. Tamburini
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  5. Zhongqing Lu
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Editors and Affiliations

  1. Middle East Technical University, Ankara, Turkey

    Emel Arinç

  2. University of Connecticut Health Center, Farmington, Connecticut, USA

    John B. Schenkman

  3. North Carolina State University, Raleigh, North Carolina, USA

    Ernest Hodgson

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Schenkman, J.B. et al. (1999). Protein-Protein Interactions in the P450 Monooxygenase System. In: Arinç, E., Schenkman, J.B., Hodgson, E. (eds) Molecular and Applied Aspects of Oxidative Drug Metabolizing Enzymes. NATO ASI Series, vol 303. Springer, Boston, MA. https://doi.org/10.1007/978-1-4615-4855-3_2

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