Affordable Access

deepdyve-link
Publisher Website

Metacaspase-3 of Plasmodium falciparum: An atypical trypsin-like serine protease.

Authors
  • Kumar, Bhumika1
  • Verma, Sonia2
  • Kashif, Mohammad3
  • Sharma, Ruby4
  • Atul,5
  • Dixit, Rajnikant2
  • Singh, Agam P3
  • Pande, Veena5
  • Saxena, Ajay K4
  • Abid, Mohammad6
  • Pandey, Kailash C7
  • 1 National Institute of Malaria Research, New Delhi, 110077, India; Department of Bioscience, Jamia Millia Islamia, New Delhi 110025, India. , (India)
  • 2 National Institute of Malaria Research, New Delhi, 110077, India. , (India)
  • 3 National Institute of Immunology, New Delhi, 110067, India. , (India)
  • 4 Jawaharlal Nehru University, New Delhi 110067, India. , (India)
  • 5 Kumaun University, Nainital, Uttarakhand, 263001, India. , (India)
  • 6 Department of Bioscience, Jamia Millia Islamia, New Delhi 110025, India. , (India)
  • 7 National Institute of Malaria Research, New Delhi, 110077, India; National Institute for Research in Environmental Health, Bhopal, 462001, India. Electronic address: [email protected] , (India)
Type
Published Article
Journal
International journal of biological macromolecules
Publication Date
Jul 10, 2019
Volume
138
Pages
309–320
Identifiers
DOI: 10.1016/j.ijbiomac.2019.07.067
PMID: 31301397
Source
Medline
Keywords
Language
English
License
Unknown

Abstract

Metacaspases are clan CD cysteine peptidases found in plants, fungi and protozoa that possess a conserved Peptidase_C14 domain, homologous to the human caspases and a catalytic His/Cys dyad. Earlier reports have indicated the role of metacaspases in cell death; however, metacaspases of human malaria parasite remains poorly understood. In this study, we aimed to functionally characterize a novel malarial protease, P. falciparum metacaspase-3 (PfMCA3). Unlike other clan CD peptidases, PfMCA3 has an atypical active site serine (Ser1865) residue in place of canonical cysteine and it phylogenetically forms a distinct branch across the species. To investigate whether this domain retains catalytic activity, we expressed, purified and refolded the Peptidase_C14 domain of PfMCA3 which was found to express in all asexual stages. PfMCA3 exhibited trypsin-like serine protease activity with ser1865 acting as catalytic residue to cleave trypsin oligopeptide substrate. PfMCA3 is inhibited by trypsin-like serine protease inhibitors. Our study found that PfMCA3 enzymatic activity was abrogated when catalytic serine1865 (S1865A) was mutated. Moreover, PfMCA3 was found to be inactive against caspase substrate. Overall, our study characterizes a novel metacaspase of P. falciparum, different from human caspases and not responsible for the caspase-like activity, therefore, could be considered as a potential chemotherapeutic target. Copyright © 2019. Published by Elsevier B.V.

Report this publication

Statistics

Seen <100 times