Biochemical characterization of plasmepsin V from Plasmodium vivax Thailand isolates: Substrate specificity and enzyme inhibition

Molecular and Biochemical Parasitology
Khomkrit SappakhawNonlawat Boonyalai

Abstract

Plasmepsin V (PMV) is a Plasmodium aspartic protease responsible for the cleavage of the Plasmodium export element (PEXEL) motif, which is an essential step for export of PEXEL containing proteins and crucial for parasite viability. Here we describe the genetic polymorphism of Plasmodium vivax PMV (PvPMV) Thailand isolates, followed by cloning, expression, purification and characterization of PvPMV-Thai, presenting the pro- and mature-form of PvPMV-Thai. With our refolding and purification method, approximately 1mg of PvPMV-Thai was obtained from 1g of washed inclusion bodies. Unlike PvPMV-Ind and PvPMV-Sal-1, PvPMV-Thai contains a four-amino acid insertion (SVSE) at residues 246-249. We have confirmed that this insertion did not interfere with the catalytic activity as it is located in the long loop (R241-E272) pointing away from the substrate-binding pocket. PvPMV-Thai exhibited similar activity to PfPMV counterparts in which PfEMP2 could be hydrolyzed more efficiently than HRPII. Substrate specificity studies at P1' showed that replacing Ser by Val or Glu of the PfEMP2 peptide markedly reduced the enzyme activity of PvPMV similar to that of PfPMV whereas replacing His by Val or Ser of the HRPII peptide increased the cleavage...Continue Reading

References

Dec 5, 1993·Journal of Molecular Biology·A Sali, T L Blundell
Aug 6, 1996·Proceedings of the National Academy of Sciences of the United States of America·E Suss-TobyG E Ward
Sep 17, 1996·Proceedings of the National Academy of Sciences of the United States of America·A M SilvaJ W Erickson
Feb 8, 2002·Nature·Louis H MillerOgobara K Doumbo
Dec 28, 2002·Journal of Virology·John ZiebuhrAlexander E Gorbalenya
Oct 27, 2004·Antimicrobial Agents and Chemotherapy·J Kevin Baird
Dec 14, 2004·Science·Matthias MartiAlan F Cowman
Apr 21, 2005·The Journal of Biological Chemistry·Lars PradeDaniel Bur
Jun 7, 2008·Molecular and Biochemical Parasitology·Henry H ChangMichael A Marletta
Aug 22, 2009·The Lancet Infectious Diseases·Ivo MuellerHernando A del Portillo
Nov 3, 2009·Trends in Parasitology·Tobias Spielmann, Tim-Wolf Gilberger
Feb 2, 2010·Molecular and Biochemical Parasitology·Andrew R OsborneKasturi Haldar
Apr 28, 2011·Journal of Structural Biology·Prasenjit BhaumikAlla Gustchina
May 5, 2011·Biochimica Et Biophysica Acta·Prasenjit BhaumikAlexander Wlodawer
Jul 20, 2011·Archives of Biochemistry and Biophysics·Huogen XiaoRickey Y Yada
Oct 1, 2011·Nature Methods·Thomas Nordahl PetersenHenrik Nielsen
Nov 20, 2012·Cell Host & Microbe·Christof GrüringTobias Spielmann
Jun 4, 2013·Current Opinion in Microbiology·Matthias Marti, Tobias Spielmann
Jul 3, 2013·Annual Review of Microbiology·Justin A Boddey, Alan F Cowman
Jul 17, 2013·Journal of Natural Products·Pakorn Wattana-amornNgampong Kongkathip
Dec 3, 2014·Molecular and Biochemical Parasitology·Huogen XiaoRickey Y Yada
May 20, 2015·Molecular and Biochemical Parasitology·Nonlawat BoonyalaiJirundon Yuvaniyama
Jul 28, 2015·Nature Structural & Molecular Biology·Anthony N HodderAlan F Cowman
Sep 4, 2015·Nature Structural & Molecular Biology·Daniel E Goldberg

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Citations

May 6, 2020·The Journal of Biological Chemistry·Armiyaw S NasamuDaniel E Goldberg

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