Pneumocystis carinii expresses an active Rtt109 histone acetyltransferase.

American Journal of Respiratory Cell and Molecular Biology
Theodore J KottomAndrew H Limper

Abstract

Species in the genus Pneumocystis can cause severe pneumonia in immune-compromised hosts. The identification of specific targets present in Pneumocystis species, but lacking in mammalian hosts, is paramount to developing new means to treat this infection. One such potential protein is Rtt109, which is a type of histone acetyltransferase (HAT) required for DNA replication in fungi, but not found in mammals. Sequence orthologues of Rtt109 are present in other fungi, but are absent in mammals, making it a potential pan-specific target against medically relevant fungi. Accordingly, we sought to identify the presence of an Rtt109 in P. carinii. A Pneumocystis carinii (Pc) Rtt109 165-bp partial sequence was initially identified from the incomplete P. carinii genome database. Subsequently, a full-length, 1,128-bp cDNA with homology to Saccharomyces cerevisiae Rtt109 (39% Basic Local Alignment Search Tool (BLASTP)) was cloned and characterized. Sequence analysis of PcRtt109 indicated that the P. carinii molecule contains the putative catalytic aspartate present in yeast. We further demonstrated that the PcRtt109 expressed in rtt109Δ S. cerevisiae cells restored H3-K56 acetylation and the sensitivity toward DNA-damaging agents of rtt109...Continue Reading

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Citations

Mar 5, 2013·Eukaryotic Cell·Ernest RadovaniJeffrey S Fillingham
Jul 29, 2015·Medical Microbiology and Immunology·Theodore J Kottom, Andrew H Limper
Jun 14, 2015·FEMS Yeast Research·Joseph H SkalskiAndrew H Limper
Apr 29, 2015·Infection and Immunity·Theodore J KottomAndrew H Limper
Apr 16, 2014·Antimicrobial Agents and Chemotherapy·Jayme L DahlinAndrew H Limper
Jun 2, 2018·Molecular Plant-microbe Interactions : MPMI·Seomun KwonYong-Hwan Lee

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