The Trypanosoma cruzi PIN1 gene encodes a parvulin peptidyl-prolyl cis/trans isomerase able to replace the essential ESS1 in Saccharomyces cerevisiae☆

Erben, Esteban; Daum, Sebastian; Téllez-Iñón, Marı́a T.

doi:10.1016/j.molbiopara.2007.03.004

Cited by 14 publications

(38 citation statements)

References 40 publications

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“…The simplest method is to complement an ess1 ts -mutant rather than use a deletion mutant, since most non-yeast labs prefer not to carry out the requisite tetrad dissection of a diploid ESS1/ ess1 Δ strain and the subsequent genetic analysis. Orthologs that complement Ess1 in budding yeast include Xenopus lavis Pin1 (unpublished data), Trypanosoma cruzi Pin1 [41], Schizosaccharomyces pombe Pin1 [42], Candida albicans Ess1 [43], and Crytococcus deformans Ess1 [44]. The yeast complementation assay has also been extremely useful to monitor the function and enzymatic activity of Ess1-related enzymes in vivo [23, 45, 46].…”

Section: Discovery Of Ess1 and Family Membersmentioning

confidence: 99%

The Ess1 prolyl isomerase: Traffic cop of the RNA polymerase II transcription cycle

Hanes

2014

Biochimica et Biophysica Acta (BBA) - Gene Regulatory Mechanism

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Ess1 is a prolyl isomerase that regulates the structure and function of eukaryotic RNA polymerase II. Ess1 works by catalyzing the cis/trans conversion of pSer5–Pro6 bonds, and to a lesser extent pSer2–Pro3 bonds, within the carboxy-terminal domain (CTD) of Rpb1, the largest subunit of RNA pol II. Ess1 is conserved in organisms ranging from yeast to humans. In budding yeast, Ess1 is essential for growth and is required for efficient transcription initiation and termination, RNA processing, and suppression of cryptic transcription. In mammals, Ess1 (called Pin1) functions in a variety of pathways, including transcription, but it is not essential. Recent work has shown that Ess1 coordinates the binding and release of CTD-binding proteins that function as co-factors in the RNA pol II complex. In this way, Ess1 plays an integral role in writing (and reading) the so-called CTD code to promote production of mature RNA pol II transcripts including non-coding RNAs and mRNAs.

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Section: Discovery Of Ess1 and Family Membersmentioning

confidence: 99%

The Ess1 prolyl isomerase: Traffic cop of the RNA polymerase II transcription cycle

Hanes

2014

Biochimica et Biophysica Acta (BBA) - Gene Regulatory Mechanism

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“…However, several Pin1-type parvulins lacking of the WW domain have been reported, such as plant Pin1s [29]. Recently, two new members of the parvulin subfamily, TbPin1 and TbPar42, were identified from Trypanosoma brucei [10], [30]. Like plant Pin1s, TbPin1 lacks the N-terminal WW domain and only contains the catalytic PPIase domain.…”

Section: Introductionmentioning

confidence: 99%

Solution Structural Analysis of the Single-Domain Parvulin TbPin1

Sun

Peng

et al. 2012

PLoS ONE

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BackgroundPin1-type parvulins are phosphorylation-dependent peptidyl-prolyl cis-trans isomerases. Their functions have been widely reported to be involved in a variety of cellular responses or processes, such as cell division, transcription, and apoptosis, as well as in human diseases including Alzheimer's disease and cancers. TbPin1 was identified as a novel class of Pin1-type parvulins from Trypanosoma brucei, containing a unique PPIase domain, which can catalyze the isomerization of phosphorylated Ser/Thr-Pro peptide bond.Methodology/Principal FindingsWe determined the solution structure of TbPin1 and performed 15N relaxation measurements to analyze its backbone dynamics using multi-dimensional heteronuclear NMR spectroscopy. The average RMSD values of the 20 lowest energy structures are 0.50±0.05 Å for backbone heavy atoms and 0.85±0.08 Å for all heavy atoms. TbPin1 adopts the typical catalytic tertiary structure of Pin1-type parvulins, which comprises a globular fold with a four-stranded anti-parallel β-sheet core surrounded by three α-helices and one 310-helix. The global structure of TbPin1 is relatively rigid except the active site. The 2D EXSY spectra illustrate that TbPin1 possesses a phosphorylation-dependent PPIase activity. The binding sites of TbPin1 for a phosphorylated peptide substrate {SSYFSG[p]TPLEDDSD} were determined by the chemical shift perturbation approach. Residues Ser15, Arg18, Asn19, Val21, Ser22, Val32, Gly66, Ser67, Met83, Asp105 and Gly107 are involved in substantial contact with the substrate.Conclusions/SignificanceThe solution structure of TbPin1 and the binding sites of the phosphorylated peptide substrate on TbPin1 were determined. The work is helpful for further understanding the molecular basis of the substrate specificity for Pin1-type parvulin family and enzyme catalysis.

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“…By performing genome-wide drug sensitivity screens (chemogenomic profiling) [12], [13], [14], [15], [16], [17] of yeast mutants with the antimalarials quinine [18], St. John's Wort [19] and artemisinin [20], researchers were able to identify their primary targets as well as identify potential side effects. Furthermore, several groups have been able to complement yeast loss-of function mutations by expressing coding sequences from parasites such as Plasmodium [21], [22], Schistosoma [23], [24], [25], Leishmania [26] or Trypanosoma [6], [27], [28], [29], [30], [31].…”

Section: Introductionmentioning

confidence: 99%

Functional Expression of Parasite Drug Targets and Their Human Orthologs in Yeast

et al. 2011

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BackgroundThe exacting nutritional requirements and complicated life cycles of parasites mean that they are not always amenable to high-throughput drug screening using automated procedures. Therefore, we have engineered the yeast Saccharomyces cerevisiae to act as a surrogate for expressing anti-parasitic targets from a range of biomedically important pathogens, to facilitate the rapid identification of new therapeutic agents.Methodology/Principal FindingsUsing pyrimethamine/dihydrofolate reductase (DHFR) as a model parasite drug/drug target system, we explore the potential of engineered yeast strains (expressing DHFR enzymes from Plasmodium falciparum, P. vivax, Homo sapiens, Schistosoma mansoni, Leishmania major, Trypanosoma brucei and T. cruzi) to exhibit appropriate differential sensitivity to pyrimethamine. Here, we demonstrate that yeast strains (lacking the major drug efflux pump, Pdr5p) expressing yeast (ScDFR1), human (HsDHFR), Schistosoma (SmDHFR), and Trypanosoma (TbDHFR and TcDHFR) DHFRs are insensitive to pyrimethamine treatment, whereas yeast strains producing Plasmodium (PfDHFR and PvDHFR) DHFRs are hypersensitive. Reassuringly, yeast strains expressing field-verified, drug-resistant mutants of P. falciparum DHFR (Pfdhfr 51I,59R,108N) are completely insensitive to pyrimethamine, further validating our approach to drug screening. We further show the versatility of the approach by replacing yeast essential genes with other potential drug targets, namely phosphoglycerate kinases (PGKs) and N-myristoyl transferases (NMTs).Conclusions/SignificanceWe have generated a number of yeast strains that can be successfully harnessed for the rapid and selective identification of urgently needed anti-parasitic agents.

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The Trypanosoma cruzi PIN1 gene encodes a parvulin peptidyl-prolyl cis/trans isomerase able to replace the essential ESS1 in Saccharomyces cerevisiae☆

Cited by 14 publications

References 40 publications

The Ess1 prolyl isomerase: Traffic cop of the RNA polymerase II transcription cycle

The Ess1 prolyl isomerase: Traffic cop of the RNA polymerase II transcription cycle

Solution Structural Analysis of the Single-Domain Parvulin TbPin1

Functional Expression of Parasite Drug Targets and Their Human Orthologs in Yeast

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