The importance of pH in regulating the function of the Fasciola hepatica cathepsin L1 cysteine protease

Jonathan Lowther, Mark W Robinson, Sheila M Donnelly, Weibo Xu, Colin M Stack, Jacqueline M Matthews, John P Dalton

Research output: Contribution to journalArticlepeer-review

56 Citations (Scopus)

Abstract

The helminth parasite Fasciola hepatica secretes cathepsin L cysteine proteases to invade its host, migrate through tissues and digest haemoglobin, its main source of amino acids. Here we investigated the importance of pH in regulating the activity and functions of the major cathepsin L protease FheCL1. The slightly acidic pH of the parasite gut facilitates the auto-catalytic activation of FheCL1 from its inactive proFheCL1 zymogen; this process was approximately 40-fold faster at pH 4.5 than at pH 7.0. Active mature FheCL1 is very stable at acidic and neutral conditions (the enzyme retained approximately 45% activity when incubated at 37 degrees C and pH 4.5 for 10 days) and displayed a broad pH range for activity peptide substrates and the protein ovalbumin, peaking between pH 5.5 and pH 7.0. This pH profile likely reflects the need for FheCL1 to function both in the parasite gut and in the host tissues. FheCL1, however, could not cleave its natural substrate Hb in the pH range pH 5.5 and pH 7.0; digestion occurred only at pH
Original languageEnglish
Article numbere369
Pages (from-to)e369
JournalPLoS Neglected Tropical Diseases
Volume3
Issue number1
DOIs
Publication statusPublished - 2009

ASJC Scopus subject areas

  • Infectious Diseases
  • Public Health, Environmental and Occupational Health
  • Pharmacology, Toxicology and Pharmaceutics(all)

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