Prp8 intein in fungal pathogens: target for potential antifungal drugs.
Inteins are self-splicing intervening sequences in proteins, and inteins of pathogenic organisms can be attractive drug targets. Here, we report an intein in important fungal pathogens including Aspergillus fumigatus, Aspergillus nidulans, Histoplasma capsulatum, and different serotypes of Cryptococcus neoformans. This intein is inside the extremely conserved and functionally essential Prp8 protein, and it varies in size from 170 aa in C. neoformans to 819 aa in A. fumigatus, which is caused by the presence or absence of an endonuclease domain and a putative tongs subdomain in the intein. Prp8 inteins of these organisms were demonstrated to do protein splicing in a recombinant protein in Escherichia coli. These findings revealed Prp8 inteins as attractive targets for potential antifungal drugs to be identified using existing selection and screening methods.
Liu
Xiang-Qin
XQ
Department of Biochemistry and Molecular Biology, Dalhousie University, Halifax, NS, Canada B3H 4H7. pxqliu@dal.ca
Yang
Jing
J
D000595:Amino Acid Sequence; D000935:Antifungal Agents / Q000494:pharmacology*; D001230:Aspergillus / Q000187:drug effects / Q000472:pathogenicity; D001483:Base Sequence; D017124:Conserved Sequence; D003455:Cryptococcus neoformans / Q000187:drug effects / Q000472:pathogenicity; D017931:DNA Primers; D004720:Endonucleases / Q000737:chemistry / Q000187:drug effects / Q000502:physiology*; D005656:Fungal Proteins / Q000737:chemistry / Q000187:drug effects / Q000502:physiology*; D006658:Histoplasma / Q000187:drug effects / Q000472:pathogenicity; D020071:Interspersed Repetitive Sequences / Q000187:drug effects / Q000502:physiology*; D008969:Molecular Sequence Data; D011994:Recombinant Proteins / Q000737:chemistry; D016415:Sequence Alignment; D017386:Sequence Homology, Amino Acid
D000935:Antifungal Agents; D017931:DNA Primers; D005656:Fungal Proteins; D011994:Recombinant Proteins; D004720:Endonucleases