Effects of amino-terminus truncation in human cytochrome P450IID6 on its insertion into the endoplasmic reticulum membrane of Saccharomyces cerevisiae.
A truncated form of cytochrome P450IID6 deprived of 22 NH2-terminal amino acids residues (P450IID6 delta 1-22) was found in both the cytosol and the microsomal fraction of the yeast, Saccharomyces cerevisiae. A reduced CO difference spectrum of this form was characterized by the absence of absorption at 448 nm and weak absorption at 420 nm. Another peculiarity of P450IID6 delta 1-22 expression was its reduced content in the yeast cells compared to that of P450IID6, with the intracellular levels of the corresponding mRNAs being the same. We suggest that the deleted form of P450IID6, i.e. lacking 22 NH2-terminal amino acid residues, is not inserted properly in the endoplasmic reticulum membrane: it does not take up the proper conformation to enable normal heme binding and is degraded in the yeast cells.
Krynetsky EYu
Chemical Faculty, M. V. Lomonosov Moscow State University, Moscow, Russian Federation.
Drutsa
V L
VL
Kovaleva
I E
IE
Luzikov
V N
VN
Uvarov VYu
D001483:Base Sequence; D019389:Cytochrome P-450 CYP2D6; D003577:Cytochrome P-450 Enzyme System / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D017931:DNA Primers; D004721:Endoplasmic Reticulum / Q000201:enzymology*; D006801:Humans; D007425:Intracellular Membranes / Q000201:enzymology; D006899:Mixed Function Oxygenases / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D008969:Molecular Sequence Data; D010446:Peptide Fragments / Q000235:genetics / Q000378:metabolism; D012333:RNA, Messenger / Q000378:metabolism; D012441:Saccharomyces cerevisiae / Q000235:genetics / Q000378:metabolism*
D017931:DNA Primers; D010446:Peptide Fragments; D012333:RNA, Messenger; D003577:Cytochrome P-450 Enzyme System; D006899:Mixed Function Oxygenases; D019389:Cytochrome P-450 CYP2D6