Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound   Target Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound

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Query: EC:3.1.30.2 (endonuclease)
18,621 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

We have used comparative sequence analysis to identify an intein-like sequence (protein splicing element) present in Cryptococcus neoformans, a fungal pathogen of humans. The sequence encoding this element is present in the C. neoformans PRP8 gene, as an in-frame insertion relative to the PRP8 genes of other organisms. It contains sequences similar to those of the protein-splicing domains of two previously described yeast inteins (in Saccharomyces cerevisiae and Candida tropicalis), although it lacks any recognizable internal endonuclease domain. The Cryptococcus neoformans intein (Cne PRP8) is only the second to be found in a eukaryote nuclear genome; the previously described yeast inteins occur at the same site in the VMA gene homologues of S. cerevisiae and C. tropicalis. The host gene of the Cryptococcus intein, PRP8, encodes a highly conserved mRNA splicing protein found as part of the spliceosome. The Cne PRP8 intein may be a useful drug target in addressing the cryptococcal infections so prevalent in AIDS patients.
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PMID:A nuclear-encoded intein in the fungal pathogen Cryptococcus neoformans. 1174 98

Only two nuclear encoded inteins have been described. The first, SceVMA, was found in a vacuolar ATPase gene of Saccharomyces cerevisiae and related yeasts. The second, CnePRP8, was found in the PRP8 gene of Cryptococcus neoformans. CnePRP8 contains protein sequences associated with intein splicing but no endonuclease domain. We compared allelic mini-inteins in both varieties of C. neoformans (var. neoformans and var. grubii) and in the related primary pathogen C. gattii to study the evolution of both the mini-intein and the host. We also describe a full-length, endonuclease-containing intein in Cryptococcus laurentii, a moderately distant relation of C. neoformans. We did not detect an intein in the PRP8 gene of other species of Cryptococcus including species closely related to the C. neoformans/C. gattii group. It is therefore probable that the C. neoformans/C. gattii mini-intein was derived from horizontal transfer in which C. laurentii or another intein-containing species was the source.
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PMID:The PRP8 inteins in Cryptococcus are a source of phylogenetic and epidemiological information. 1580 9

Until recently the only intein known to be encoded by the nuclear genome of a eukaryote was the VMA intein in the vacuolar ATPase precursor of several species of saccharomycete yeast. This intein has been intensively studied and much information has been gained about its structure, mode of action and evolutionary history. We recently reported a second nuclear intein, Cne PRP8, encoded within the PRP8 gene of the basidiomycete Cryptococcus neoformans. Subsequent studies have found allelic PRP8 inteins in several species of yeast and filamentous ascomycetes. Here we report two further, non-allelic, inteins from ascomycete species. The yeast Debaryomyces hansenii (which also has a VMA intein) has an intein encoded within the sequence of the glutamate synthase gene (GLT1). There are also inteins encoded in the homologous GLT1 genes of the yeast Candida (Pichia) guilliermondii and the filamentous fungus Podospora anserina. These allelic GLT1 inteins occupy exactly the same site in the glutamate synthase and all contain domains that indicate the presence of a homing endonuclease (HEG). Podospora anserina, in addition, contains a second, non-allelic, intein encoded in the chitin synthase gene (CHS2); this intein also contains a HEG domain. We describe the phylogenetic relationships among the four eukaryote nuclear encoded inteins (VMA, PRP8, GLT1 and CHS2). We also consider this phylogeny in the broader context of eubacterial, archaeal and eukaryote viral and organelle inteins.
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PMID:Two new fungal inteins. 1584 95

Inteins are protein-intervening sequences found inside the coding region of different host proteins and are translated in-frame with them. They can self-excise through protein splicing, which ligates the host protein flanks with a peptide bond. In this study, four different species of the genus Penicillium were investigated for the presence of inteins inside the conserved splicing-factor protein PRP8. We identified 157 to 162 amino acid in-frame insertions in the PRP8 protein of Penicillium chrysogenum, Penicillium expansum, and Penicillium vulpinum (formerly Penicillium claviforme). The Penicillium PRP8 inteins are mini-inteins without a conserved endonuclease domain. We demonstrated that the PRP8 mini-inteins of P. chrysogenum, P. expansum, and P. vulpinum undergo autocatalytic protein splicing when heterologously expressed in E. coli, in a model host protein, and in a divided GFP model system. They are, thus, among the smallest known nuclear-encoded, active splicing protein elements. The GFP assay should be valuable as a screening system for protein splicing inhibitors as potential antimycotic agents and as tools for studying the mechanism of protein splicing of fungal mini-inteins.
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PMID:Protein splicing of PRP8 mini-inteins from species of the genus Penicillium. 1654 41

Self splicing introns and inteins that rely on a homing endonuclease for propagation are parasitic genetic elements. Their life-cycle and evolutionary fate has been described through the homing cycle. According to this model the homing endonuclease is selected for function only during the spreading phase of the parasite. This phase ends when the parasitic element is fixed in the population. Upon fixation the homing endonuclease is no longer under selection, and its activity is lost through random processes. Recent analyses of these parasitic elements with functional homing endonucleases suggest that this model in its most simple form is not always applicable. Apparently, functioning homing endonuclease can persist over long evolutionary times in populations and species that are thought to be asexual or nearly asexual. Here we review these recent findings and discuss their implications. Reasons for the long-term persistence of a functional homing endonuclease include: More recombination (sexual and as a result of gene transfer) than previously assumed for these organisms; complex population structures that prevent the element from being fixed; a balance between active spreading of the homing endonuclease and a decrease in fitness caused by the parasite in the host organism; or a function of the homing endonuclease that increases the fitness of the host organism and results in purifying selection for the homing endonuclease activity, even after fixation in a local population. In the future, more detailed studies of the population dynamics of the activity and regulation of homing endonucleases are needed to decide between these possibilities, and to determine their relative contributions to the long term survival of parasitic genes within a population. Two outstanding publications on the amoeba Naegleria group I intron (Wikmark et al. BMC Evol Biol 2006, 6:39) and the PRP8 inteins in ascomycetes (Butler et al.BMC Evol Biol 2006, 6:42) provide important stepping stones towards integrated studies on how these parasitic elements evolve through time together with, or despite, their hosts.
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PMID:Inteins, introns, and homing endonucleases: recent revelations about the life cycle of parasitic genetic elements. 1710 Oct 53

Inteins are internal protein splicing elements that can autocatalytically self-excise from their host protein and ligate the protein flanks (exteins) with a peptide bond. Large inteins comprise independent protein splicing and endonuclease domains whereas mini-inteins lack the central endonuclease domain. To identify mini-intein domains that are essential for protein splicing, deletions were introduced at different sites of the 157-aa PRP8 mini-intein of Penicillium chrysogenum. The removal of eight and six amino acids at two different sites resulted in a functional eukaryotic mini-intein of only 143 aa.
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PMID:Minimization of a eukaryotic mini-intein. 1805 28

Inteins are protein-intervening sequences that are translated with the host protein and can self-excise themselves post-translationally in an autocatalytic process. The flanking regions--called exteins--are then re-ligated with a new peptide bond, resulting in a mature host protein. Previously, we have identified inteins in the highly conserved 3.2 region of the PRP8 protein from species of the genus Penicillium. These inteins are integrated at the same position as that which has recently been described in PRP8 proteins from different strains of Cryptococcus neoformans and several ascomycetes. In this study, we investigated the presence of PRP8 inteins in four members of the genus Eupenicillium. Two species of this genus, Eupenicillium crustaceum and Eupenicillium baarnense, contain an intein at the same insertion site. Both inteins are mini-inteins and undergo self-splicing when heterologously expressed with a model host protein in Escherichia coli. Interestingly, we identified introns in the prp8-sequence encoding the 3.2 regions of the PRP8 protein in Eupenicillium meridianum and Eupenicillium terrenum. The introns are located 13 bps and 15 bps downstream of the putative intein insertion site. Here, we consider that the lack of inteins in these two species might be due to the prevention of endonuclease-mediated intein propagation in the intron-containing prp8-sequences.
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PMID:Inteins and introns within the prp8 -gene of four Eupenicillium species. 1925 33

Strains of Botrytis cinerea are polymorphic for the presence of an intein in the Prp8 gene (intein +/-). The intein encodes a homing endonuclease (HEG). During meiosis in an intein +/- heterozygote, the homing endonuclease initiates intein 'homing' by inducing gene conversion. In such meioses, the homing endonuclease triggers gene conversion of the intein together with its flanking sequences into the empty allele. The efficiency of gene conversion of the intein was found to be 100%. The extent of flanking sequence affected by the gene conversion varied in different meioses. A survey of the inteins and flanking sequences of a group B. cinerea isolates indicates that there are two distinct variants of the intein both of which have active HEGs. The survey also suggests that the intein has been actively homing during the evolution of the species and that the PRP8 intein may have entered the species by horizontal transfer.
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PMID:Sexual mating of Botrytis cinerea illustrates PRP8 intein HEG activity. 2009 92

Inteins are intervening sequences that are transcribed and translated with flanking host protein sequences and then self-excised by protein splicing. Bi-functional inteins also contain a homing endonuclease responsible for their genetic mobility. The PRP8 intein, the most widespread among fungi, occurs in important pathogens such as Histoplasma capsulatum and Paracoccidioides brasiliensis, from the Ajellomycetaceae family. Herein, we describe the bi-functional PRP8 intein in two other Ajellomycetacean pathogens, Blastomyces dermatitidis and Emmonsia parva. Sequence analysis and experimental evidence suggest that the homing endonuclease from PbrPRP8 is inactive. The splicing activity of the PRP8 intein from the B. dermatitidis, E. parva and P. brasiliensis species complex was demonstrated in a non-native protein context in Escherichia coli. Since the PRP8 intein is located in a functionally essential nuclear protein, it can be considered a promising therapeutic target for anti-fungal drugs, because inhibition of intein splicing should inhibit proliferation of intein-containing pathogens.
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PMID:PRP8 intein in Ajellomycetaceae family pathogens: sequence analysis, splicing evaluation and homing endonuclease activity. 2068 55

The mobile elements termed inteins have a sporadic distribution in microorganisms. It is unclear how these elements are maintained. Inteins are intervening protein sequences that autocatalytically excise themselves from a precursor. Excision is a post-translational process referred to as 'protein splicing' in which the sequences flanking the intein are ligated, reforming the mature host protein. Some inteins contain a homing endonuclease domain (HEG) that is proposed to facilitate propagation of the intein element within a gene pool. We have previously demonstrated that the HEG of the PRP8 intein is highly active during meiosis in Botrytis cinerea. Here we analysed the Prp8 gene status in 21 additional Botrytis species to obtain insight into the mode of intein inheritance within the Botrytis lineage. Of the 21 species, 15 contained a PRP8 intein whereas six did not. The analysis was extended to closely related (Sclerotiniaceae) and distantly related (Ascomycota) taxa, focussing on evolutionary diversification of the PRP8 intein, including their possible acquisition by horizontal transfer and loss by deletion. Evidence was obtained for the occurrence of genetic footprints of previous intein occupation. There is no compelling evidence of horizontal transfer among species. Three distinct states of the Prp8 allele were identified, distributed over different orders within the Ascomycota: an occupied allele; an empty allele that was never occupied; an empty allele that was presumably previously occupied, from which the intein was precisely deleted. The presence of the genetic footprint identifies 20 species (including Neurospora crassa, Magnaporthe oryzae and Fusarium oxysporum) that previously contained the intein but have lost it entirely, while only 18 species (including Podospora anserina and Fusarium graminearum) appear never to have contained a PRP8 intein. The analysis indicates that inteins may be maintained in an equilibrium state.
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PMID:PRP8 inteins in species of the genus Botrytis and other ascomycetes. 2228 71


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