Identification of unique amino acids that modulate CYP4A7 activity.

  title={Identification of unique amino acids that modulate CYP4A7 activity.},
  author={P A Loughran and Linda J. Roman and Alastair Aitken and R. T. Miller and Bettie Sue Siler Masters},
  volume={39 49},
A multifamily sequence alignment of the rabbit CYP4A members with the known structure of CYP102 indicates amino acid differences falling within the so-called substrate recognition site(s) (SRS). Chimeric proteins constructed between CYP4A4 and CYP4A7 indicate that laurate activity is affected by the residues within SRS1 and prostaglandin activity is influenced by SRS2-3. Site-directed mutant proteins of CYP4A7 found laurate and arachidonate activity markedly diminished in the R90W mutant (SRS1… Expand
The effect of mutation of F87 on the properties of CYP102A1-CYP4C7 chimeras: altered regiospecificity and substrate selectivity
The results show that chimeragenesis involving only the second half of SRS-1 plus F87 is sufficient to change the substrate selectivity of CYP102A1 from fatty acids to farnesol and to produce a single primary product. Expand
Alternative splicing determines the function of CYP4F3 by switching substrate specificity.
The results establish that tissue-specific alternative splicing of pre-mRNA can be used as a mechanism for changing substrate specificity and increasing the functional diversity of cytochrome P450 genes. Expand
Scanning chimeragenesis: the approach used to change the substrate selectivity of fatty acid monooxygenase CYP102A1 to that of terpene ω-hydroxylase CYP4C7
A procedure is developed which uses the known structure of the substrate-bound heme domain of CYP102A1 and its sequence homology with a cytochrome P450 of unknown structure, both of which react with a common substrate but produce different products, to create recombinant enzymes which have substrate selectivity different from that of CYPs 102A1. Expand
Sequence analysis of novel CYP4 transcripts from Mytilus galloprovincialis.
The results suggest the great expansion of the CYP4Y cDNAs indicative of CYP 4 proteins in the mussel M. galloprovincialis presumably as a response to different environmental conditions. Expand
Oxygenation of polyunsaturated long chain fatty acids by recombinant CYP4F8 and CYP4F12 and catalytic importance of Tyr-125 and Gly-328 of CYP4F8.
It is concluded that CYP4F8 and CYF4F12 catalyze epoxidation of 22:6n-3 and 22:5n- 3, and CYP 4F8 omega3-hydroxylation of 22?:5n -6, and single amino acid substitutions in SRS-1 and SRS -4 of CYP3F8 may influence oxygenation of certain substrates. Expand
Expressed CYP4A4 metabolism of prostaglandin E(1) and arachidonic acid.
The enzyme was purified, and its activity with substrates prostaglandin E(1) (PGE(1)) and AA was examined, and a conformational change occurred in CYP4A4 protein upon binding of cyt b(5) or apo b( 5). Expand
Investigating the industrial application potentials ofcytochrome P450 BM-3 and four novel putativecytochrome P450s isolated from Cupriavidus necatorH16
Cytochrome P450 is a superfamily of heme-dependent monooxygenases. These enzymes play a very important role in drug metabolism and detoxification since they catalyse a broad range of reactionsExpand
Allosteric phenomena in cytochrome P450-catalyzed monooxygenations.
Dioxygen binding to cytochrome P450 displays nonhyperbolic kinetic profiles in the presence of certain substrates; the latter, together with redox proteins such as cy tochrome b5, can exert efficient control of the abortive breakdown of the oxyferrous intermediates formed. Expand
Very high conservation between Cyp6a2 from Drosophila melanogaster and its ortholog Cyp6a26 from D. simulans
Immunohistochemistry experiments of phenobarbital‐treated adult drosophila show that the spatial expression pattern of the two proteins is also conserved between the two species, arguing in favor of the conservation of the function of these homologous genes between theTwo Drosophila species. Expand
Studies on Cytochrome P450 4X1
Antisera raised against recombinant human CYP4Z1, mouse Aryl hydrocarbon receptor (AhR), and C.elegans Latrophilin (LpH) proteins were titred over the course of several bleeds, and quantification showed that this is a major cytochrome P450 in brain. Expand