Importance of the proline-rich region following signal-anchor sequence in the formation of correct conformation of microsomal cytochrome P-450s.

Importance of the proline-rich region following signal-anchor sequence in the formation of correct conformation of microsomal cytochrome P-450s. Research Abstract Details 

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Importance of the proline-rich region following signal-anchor sequence in the formation of correct conformation of microsomal cytochrome P-450s. Abstract Text:

S Yamazaki,K Sato,K Suhara,M Sakaguchi,K Mihara,T Omura,

A proline-rich region is present following the signal-anchor sequence in the amino-terminal portion of all known microsomal cytochrome P-450s. To assess the functional significance of the proline residues in this region, we systematically altered these residues of cytochrome P450(M1) (P450 2C11); one, two, and three proline residues out of the five in the region were exchanged for alanine residues. The wild-type and the mutated proteins were expressed in the fission yeast Schizosaccharomyces pombe under the control of nmt1 promoter. The wild-type and the mutated proteins were all highly expressed in the yeast cells (5-9% of the total membrane protein). The expressed wild-type P450(M1) showed a typical carbon monoxide difference spectrum of P-450 and the activity of testosterone hydroxylation, whereas all the mutated proteins constructed in the present study showed no characteristic P-450 spectrum, suggesting that the substitution of the proline residues in this region resulted in a defect of proper heme incorporation. Furthermore, the mutated proteins in which more than one proline residues had been exchanged were more sensitive to trypsin digestion than the wild type. From these results, we propose that the proline residues in the proline-rich region are crucial for the formation of the correct conformation of microsomal P-450 molecules.

Importance of the proline-rich region following signal-anchor sequence in the formation of correct conformation of microsomal cytochrome P-450s. Publishing Authors By Initials

S Yamazaki,K Sato,K Suhara,M Sakaguchi,K Mihara,T Omura,

For similar polycyclic compounds: steroids: androstanes: androstenes: androstenols: testosterone research abstracts see: polycyclic compounds: steroids: androstanes: androstenes: androstenols: testosterone research

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Importance of the proline-rich region following signal-anchor sequence in the formation of correct conformation of microsomal cytochrome P-450s. Journal Published:

PUBLICATION TYPE: Research Support, Non-U.S. Gov

Journal: Journal of biochemistry

VOLUME: 114

Page Numbers: 652-7

Journal Abbreviation: J. Biochem.

ISSN: 0021-924X

DAY: 19

MONTH: Nov

YEAR: 1993

Importance of the proline-rich region following signal-anchor sequence in the formation of correct conformation of microsomal cytochrome P-450s. Information

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LANGUAGE: eng

NlmUniqueID: 376600

Importance of the proline-rich region following signal-anchor sequence in the formation of correct conformation of microsomal cytochrome P-450s. Keywords Mesh Terms:

KEYWORDS: Testosterone

MESH TERMS: metabolism

Chemical & Substance for Abstract: Importance of the proline-rich region following signal-anchor sequence in the formation of correct conformation of microsomal cytochrome P-450s. Information

Substance Name: Steroid 16-alpha-Hydroxylase

Registry Number: EC 1.14.14.1

Grant and Affiliation Information for Importance of the proline-rich region following signal-anchor sequence in the formation of correct conformation of microsomal cytochrome P-450s.

AFFILIATION: Department of Molecular Biology, Graduate School of Medical Science, Kyushu University, Fukuoka.

Country: JAPAN

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MEDLINETA: J Biochem

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