Structural Genomics of Pathogenic Protozoa: an Overview

Fan, Erkang; Baker, David; Fields, Stanley; Gelb, Michael H.; Buckner, Frederick S.; Voorhis, Wesley C. Van; Phizicky, Eric M.; Dumont, Mark E.; Mehlin, Christopher; Grayhack, Elizabeth J.; Sullivan, Mark A.; Verlinde, Christophe L. M. J.; DeTitta, George T.; Meldrum, Deirdre R.; Merritt, E.A.; Earnest, Thomas; Soltis, M.; Zucker, Frank; Myler, Peter J.; Schoenfeld, Lori W.; Kim, David E.; Worthey, Liz; LaCount, Doug; Vignali, Marissa; Li, Jizhen; Mondal, Somnath; Massey, Archna P.; Carroll, Brian; Gulde, Stacey; Luft, Joseph R.; DeSoto, Larry A.; Holl, Mark R.; Caruthers, J.M.; Bosch, Jürgen; Robien, M.A.; Arakaki, T.L.; Holmes, Michael; Trong, I. Le; Hól, Wim G. J.

doi:10.1007/978-1-60327-058-8_33

Cited by 38 publications

(35 citation statements)

References 31 publications

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“…TveIF5A share 37% identity with eIF5A from Leishmania mexicana . We thus generated a 3D model of TveIF5A using eIF5A from L. mexicana (PDB: 1XTD) [13] as the template. According to the 3D model, the phosphorylated residues T55 and T82 are near K57 (Figure 3 B ).…”

Section: Resultsmentioning

confidence: 99%

Identification of the Phosphorylated Residues in TveIF5A by Mass Spectrometry

Quintas-Granados¹,

López-Camarillo²,

Armas³

et al. 2013

Genomics, Proteomics &Amp; Bioinformatics

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The initiation factor eIF5A in Trichomonas vaginalis (TveIF5A) is previously shown to undergo hypusination, phosphorylation and glycosylation. Three different pI isoforms of TveIF5A have been reported. The most acidic isoform (pI 5.2) corresponds to the precursor TveIF5A, whereas the mature TveIF5A appears to be the most basic isoform (pI 5.5). In addition, the intermediary isoform (pI 5.3) is found only under polyamine-depleted conditions and restored with exogenous putrescine. We propose that differences in PI are due to phosphorylation of the TveIF5A isoforms. Here, we have identified phosphorylation sites using mass spectrometry. The mature TveIF5A contains four phosphorylated residues (S3, T55, T78 and T82). Phosphorylation at S3 and T82 is also identified in the intermediary TveIF5A, while no phosphorylated residues are found in the precursor TveIF5A. It has been demonstrated that eIF5A proteins from plants and yeast are phosphorylated by a casein kinase 2 (CK2). Interestingly, a gene encoding a protein highly similar to CK2 (TvCK2) is found in T. vaginalis, which might be involved in the phosphorylation of TveIF5A in T. vaginalis.

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Section: Resultsmentioning

confidence: 99%

Identification of the Phosphorylated Residues in TveIF5A by Mass Spectrometry

Quintas-Granados¹,

López-Camarillo²,

Armas³

et al. 2013

Genomics, Proteomics &Amp; Bioinformatics

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“…The knowledge of parasite biology as well as the availability of the whole genomes and proteomics provides a wide range of novel targets for drug design [51][52][53][54]. The wealth of information generated by these experiments has created the need for robust and reliable data processing methods to analyze and identify relevant molecular targets.…”

Section: Molecular Targets For Drug Designmentioning

confidence: 99%

Structure-Based Drug Discovery for Tropical Diseases

Güido

Oliva

2009

CTMC

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Parasitic diseases are amongst the foremost threats to human health and welfare around the world. In tropical and subtropical regions of the world, the consequences of parasitic infections are devastating both in terms of human morbidity and mortality. The current available drugs are limited, ineffective, and require long treatment regimens. To overcome these limitations, the identification of new macromolecular targets and small-molecule modulators is of utmost importance. The advances in genomics and proteomics have prompted drug discovery to move toward more rational strategies. The increasing understanding of the fundamental principles of protein-ligand interactions combined with the availability of compound libraries has facilitated the identification of promising hits and the generation of high quality lead compounds for tropical diseases. This review presents the current progresses and applications of structure-based drug design (SBDD) for the discovery of innovative chemotherapy agents for a variety of parasitic diseases, highlighting the challenges, limitations, and future perspectives in medicinal chemistry.

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“…Through the rapid progress of structural genomics, a vast number of structures have been recently determined for hypothetical proteins identified by genome projects (5). By proposing molecular and cellular functions for unannotated proteins, structural genomics studies of human pathogens have been useful in identifying potential drug targets and in providing critical information for structure-based drug discovery (6)(7)(8)(9)(10). In particular, NMR spectroscopy has been employed efficiently for both structural genomics (11)(12)(13) and structure-based drug discovery efforts (14)(15)(16)(17), by monitoring protein structures in a solution state.…”

Section: Introductionmentioning

confidence: 99%