The P450 Superfamily: Update on New Sequences, Gene Mapping, Accession Numbers, Early Trivial Names of Enzymes, and Nomenclature

Abstract

We provide here a list of 221 P450 genes and 12 putative pseudogenes that have been characterized as of December 14, 1992. These genes have been described in 31 eukaryotes (including 11 mammalian and 3 plant species) and 11 prokaryotes. Of 36 gene families so far described, 12 families exist in all mammals examined to date. These 12 families comprise 22 mammalian subfamilies, of which 17 and 15 have been mapped in the human and mouse genome, respectively. To date, each subfamily appears to represent a cluster of tightly linked genes. This revision supersedes the previous updates [Nebert et al., DNA 6, 1-11, 1987; Nebert et al., DNA 8, 1-13, 1989; Nebert et al., DNA Cell Biol. 10, 1-14 (1991)] in which a nomenclature system, based on divergent evolution of the superfamily, has been described. For the gene and cDNA, we recommend that the italicized root symbol "CYP" for human ("Cyp" for mouse), representing "cytochrome P450," be followed by an Arabic number denoting the family, a letter designating the subfamily (when two or more exist), and an Arabic numeral representing the individual gene within the subfamily. A hyphen should precede the final number in mouse genes. "P" ("p" in mouse) after the gene number denotes a pseudogene. If a gene is the sole member of a family, the subfamily letter and gene number need not be included. We suggest that the human nomenclature system be used for all species other than mouse. The mRNA and enzyme in all species (including mouse) should include all capital letters, without italics or hyphens. This nomenclature system is identical to that proposed in our 1991 update. Also included in this update is a listing of available data base accession numbers for P450 DNA and protein sequences. We also discuss the likelihood that this ancient gene superfamily has existed for more than 3.5 billion years, and that the rate of P450 gene evolution appears to be quite nonlinear. Finally, we describe P450 genes that have been detected by expressed sequence tags (ESTs), as well as the relationship between the P450 and the nitric oxide synthase gene superfamilies, as a likely example of convergent evolution.

Expression of cytochrome P450 CYP1B1 in breast cancer

“…The P450s are a multigene superfamily of constitutive and inducible enzymes which play a central role in the oxidative metabolism of a diverse range of xenobiotics, including carcinogens, therapeutic drugs and several groups of biologically active endogenous compounds, such as steroid hormones and fatty acids [1][2][3][4][5]. The major families of P450 involved in xenobiotic metabolism each consist of several individual forms with specific regulatory mechanisms and substrate specificities [6].…”

Role of Clinical Pharmacist to Reduce Risk in Patients Involving Antiretroviral Drugs at Abidjan Cohort

“…Pharmacodynamics interactions alter the pharmacologic response to a drug. The response can be additive, synergistic, or antagonistic [23] So, by using scientific knowledge and judgement, the clinical pharmacist may be finally improve care in resource-poor settings by the detection and the management of patient's therapeutic problems [24].…”

Cinnamate 4‐hydroxylase from Catharanthus roseus and a strategy for the functional expression of plant cytochrome P450 proteins as translational fusions with P450 reductase in Escherichia coli

“…In particular with P450, however, this could not be taken for granted because even a single AA difference can lead to drastic changes in the substrate specificity of P450 (reviewed in [1]). The heterologous expression was essential to confirm the tentative identification, and it also was an excellent possibility to investigate whether the fusion protein strategy can be used for the functional expression of plant P450 in E. coli.…”

“…Abbreviations: AA, amino acids; C4H, cinnamate 4-hydroxylase (EC 1.14.13.11); P450, cytochrome P450-dependent enzyme(s) (recommended name heme-thiolate proteins [1]); P4s0-RED, cytochrome P450 reductase(s) (EC 1.6.2.4); PCR, polymerase chain reaction.…”

“…coli had apparently not been used for plant P450, although it represents one of the simplest systems for cloning and expression. One of the reasons may be that these bacteria lack P450 activities [1] and thus also the characteristic cytochrome P4s0 reductase (P45o-RED) that is necessary for P45o function. Results with some animal P450 suggested that it may be replaced by the combined action of two soluble E. coli flavoproteins [10,11], but a high efficiency required purified proteins [12], and the general applicability was not investigated.…”