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Structures of type 2 peroxisomal targeting signals in two trypanosomatid aldolases.

Chudzik DM, Michels PA, de Walque S, Hol WG
J Mol Biol 300 697-707 (2000)
Cited: 44 times
EuropePMC logo PMID: 10891264

Abstract

Trypanosomatids, unicellular organisms responsible for several global diseases, contain unique organelles called glycosomes in which the first seven glycolytic enzymes are sequestered. We report the crystal structures of glycosomal fructose-1,6-bisphosphate aldolase from two major tropical pathogens, Trypanosoma brucei and Leishmania mexicana, the causative agents of African sleeping sickness and one form of leishmaniasis, respectively. Unlike mammalian aldolases, the T. brucei and L. mexicana aldolases contain nonameric N-terminal type 2 peroxisomal targeting signals (PTS2s) to direct their import into the glycosome. In both tetrameric trypanosomatid aldolases, the PTS2s from two different subunits form two closely intertwined structures. These "PTS2 dimers", which have very similar conformations in the two aldolase structures, are the first reported conformations of a glycosomal or peroxisomal PTS2, and provide opportunities for the design of trypanocidal compounds.

Reviews - 1f2j mentioned but not cited (1)

  1. Supramolecular enzyme-mimicking catalysts self-assembled from peptides. Liu Q, Kuzuya A, Wang ZG. iScience 26 105831 (2023)

Articles - 1f2j mentioned but not cited (7)

  1. Landscapes of Protein Posttranslational Modifications of African Trypanosoma Parasites. Zhang N, Jiang N, Zhang K, Zheng L, Zhang D, Sang X, Feng Y, Chen R, Yang N, Wang X, Cheng Z, Suo X, Lun Z, Chen Q. iScience 23 101074 (2020)
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Reviews citing this publication (12)

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  3. Recent developments in drug discovery for leishmaniasis and human African trypanosomiasis. Nagle AS, Khare S, Kumar AB, Supek F, Buchynskyy A, Mathison CJ, Chennamaneni NK, Pendem N, Buckner FS, Gelb MH, Molteni V. Chem Rev 114 11305-11347 (2014)
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Articles citing this publication (24)

  1. In silico prediction of the glycosomal enzymes of Leishmania major and trypanosomes. Opperdoes FR, Szikora JP. Mol Biochem Parasitol 147 193-206 (2006)
  2. Evolution of energy metabolism and its compartmentation in Kinetoplastida. Hannaert V, Bringaud F, Opperdoes FR, Michels PA. Kinetoplastid Biol Dis 2 11 (2003)
  3. Drug targets in Leishmania. Chawla B, Madhubala R. J Parasit Dis 34 1-13 (2010)
  4. Functional similarity between the peroxisomal PTS2 receptor binding protein Pex18p and the N-terminal half of the PTS1 receptor Pex5p. Schäfer A, Kerssen D, Veenhuis M, Kunau WH, Schliebs W. Mol Cell Biol 24 8895-8906 (2004)
  5. Characterization of glycolytic enzymes--rAldolase and rEnolase of Leishmania donovani, identified as Th1 stimulatory proteins, for their immunogenicity and immunoprophylactic efficacies against experimental visceral leishmaniasis. Gupta R, Kumar V, Kushawaha PK, Tripathi CP, Joshi S, Sahasrabuddhe AA, Mitra K, Sundar S, Siddiqi MI, Dube A. PLoS One 9 e86073 (2014)
  6. Conformational changes in Leishmania mexicana glyceraldehyde-3-phosphate dehydrogenase induced by designed inhibitors. Suresh S, Bressi JC, Kennedy KJ, Verlinde CL, Gelb MH, Hol WG. J Mol Biol 309 423-435 (2001)
  7. Inhibitors of PEX14 disrupt protein import into glycosomes and kill Trypanosoma parasites. Dawidowski M, Emmanouilidis L, Kalel VC, Tripsianes K, Schorpp K, Hadian K, Kaiser M, Mäser P, Kolonko M, Tanghe S, Rodriguez A, Schliebs W, Erdmann R, Sattler M, Popowicz GM. Science 355 1416-1420 (2017)
  8. An Anti-proteome Nanobody Library Approach Yields a Specific Immunoassay for Trypanosoma congolense Diagnosis Targeting Glycosomal Aldolase. Odongo S, Sterckx YG, Stijlemans B, Pillay D, Baltz T, Muyldermans S, Magez S. PLoS Negl Trop Dis 10 e0004420 (2016)
  9. Farnesyl diphosphate synthase is a cytosolic enzyme in Leishmania major promastigotes and its overexpression confers resistance to risedronate. Ortiz-Gómez A, Jiménez C, Estévez AM, Carrero-Lérida J, Ruiz-Pérez LM, González-Pacanowska D. Eukaryot Cell 5 1057-1064 (2006)
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  11. Organelle and translocatable forms of glyoxysomal malate dehydrogenase. The effect of the N-terminal presequence. Cox B, Chit MM, Weaver T, Gietl C, Bailey J, Bell E, Banaszak L. FEBS J 272 643-654 (2005)
  12. Structure of a class I tagatose-1,6-bisphosphate aldolase: investigation into an apparent loss of stereospecificity. LowKam C, Liotard B, Sygusch J. J Biol Chem 285 21143-21152 (2010)
  13. Ribose 5-phosphate isomerase B knockdown compromises Trypanosoma brucei bloodstream form infectivity. Loureiro I, Faria J, Clayton C, Macedo-Ribeiro S, Santarém N, Roy N, Cordeiro-da-Siva A, Tavares J. PLoS Negl Trop Dis 9 e3430 (2015)
  14. Anomalous differences of light elements in determining precise binding modes of ligands to glycerol-3-phosphate dehydrogenase. Choe J, Suresh S, Wisedchaisri G, Kennedy KJ, Gelb MH, Hol WG. Chem Biol 9 1189-1197 (2002)
  15. Glycerol 3-phosphate alters Trypanosoma brucei hexokinase activity in response to environmental change. Dodson HC, Morris MT, Morris JC. J Biol Chem 286 33150-33157 (2011)
  16. Molecular characterization of the hexokinase gene from Leishmania major. Umasankar PK, Jayakumar PC, Shouche YS, Patole MS. J Parasitol 91 1504-1509 (2005)
  17. The 6-phosphogluconate dehydrogenase from Trypanosoma cruzi: the absence of two inter-subunit salt bridges as a reason for enzyme instability. Esteve MI, Cazzulo JJ. Mol Biochem Parasitol 133 197-207 (2004)
  18. The krebs cycle enzyme α-ketoglutarate decarboxylase is an essential glycosomal protein in bloodstream African trypanosomes. Sykes S, Szempruch A, Hajduk S. Eukaryot Cell 14 206-215 (2015)
  19. The structure of the deacetylase domain of Escherichia coli PgaB, an enzyme required for biofilm formation: a circularly permuted member of the carbohydrate esterase 4 family. Nishiyama T, Noguchi H, Yoshida H, Park SY, Tame JR. Acta Crystallogr D Biol Crystallogr 69 44-51 (2013)
  20. Crystal structure of phosphoglucose isomerase from Trypanosoma brucei complexed with glucose-6-phosphate at 1.6 A resolution. Arsenieva D, Appavu BL, Mazock GH, Jeffery CJ. Proteins 74 72-80 (2009)
  21. Modeling the interaction between aldolase and the thrombospondin-related anonymous protein, a key connection of the malaria parasite invasion machinery. Buscaglia CA, Hol WG, Nussenzweig V, Cardozo T. Proteins 66 528-537 (2007)
  22. Homology modeling and molecular dynamics study of NAD-dependent glycerol-3-phosphate dehydrogenase from Trypanosoma brucei rhodesiense, a potential target enzyme for anti-sleeping sickness drug development. Zubrzycki IZ. Biophys J 82 2906-2915 (2002)
  23. Analysis of the Leishmania peroxin 7 interactions with peroxin 5, peroxin 14 and PTS2 ligands. Pilar AV, Strasser R, McLean J, Quinn E, Cyr N, Hojjat H, Kottarampatel AH, Jardim A. Biochem J 460 273-282 (2014)
  24. A Small Molecule Inhibitor of Pex3-Pex19 Interaction Disrupts Glycosome Biogenesis and Causes Lethality in Trypanosoma brucei. Banerjee H, LaPointe P, Eitzen G, Rachubinski RA. Front Cell Dev Biol 9 703603 (2021)


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