Aminopeptidase N1 (EtAPN1), an M1 metalloprotease of the apicomplexan parasite Eimeria tenella, participates in parasite development

Simon Gras, Anna Byzia, Florence B Gilbert, Sheena McGowan, Marcin Drag, Anne Silvestre, Alisson Niepceron, Fabien Lecaille, Gilles Lalmanach, Fabien Brossier

Research output: Contribution to journalArticleResearchpeer-review

Abstract

Aminopeptidases N are metalloproteases of the M1 family that have been reported in numerous apicomplexan parasites, including Plasmodium, Toxoplasma, Cryptosporidium, and Eimeria. While investigating the potency of aminopeptidases as therapeutic targets against coccidiosis, one of the most important avian diseases caused by the genus Eimeria, we identified and characterized Eimeria tenella aminopeptidase N1 (EtAPN1). Its inhibition by bestatin and amastatin, as well as its reactivation by divalent ions, is typical of zinc-dependent metalloproteases. EtAPN1 shared a similar sequence, three-dimensional structure, and substrate specificity and similar kinetic parameters with A-M1 from Plasmodium falciparum (PfA-M1), a validated target in the treatment of malaria. EtAPN1 is synthesized as a 120-kDa precursor and cleaved into 96-, 68-, and 38-kDa forms during sporulation. Further, immunolocalization assays revealed that, similar to PfA-M1, EtAPN1 is present during the intracellular life cycle stages in both the parasite cytoplasm and the parasite nucleus. The present results support the hypothesis of a conserved role between the two aminopeptidases, and we suggest that EtAPN1 might be a valuable target for anticoccidiosis drugs.
Original languageEnglish
Pages (from-to)884 - 895
Number of pages12
JournalEukaryotic Cell
Volume13
Issue number7
DOIs
Publication statusPublished - 2014

Cite this

Gras, Simon ; Byzia, Anna ; Gilbert, Florence B ; McGowan, Sheena ; Drag, Marcin ; Silvestre, Anne ; Niepceron, Alisson ; Lecaille, Fabien ; Lalmanach, Gilles ; Brossier, Fabien. / Aminopeptidase N1 (EtAPN1), an M1 metalloprotease of the apicomplexan parasite Eimeria tenella, participates in parasite development. In: Eukaryotic Cell. 2014 ; Vol. 13, No. 7. pp. 884 - 895.
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abstract = "Aminopeptidases N are metalloproteases of the M1 family that have been reported in numerous apicomplexan parasites, including Plasmodium, Toxoplasma, Cryptosporidium, and Eimeria. While investigating the potency of aminopeptidases as therapeutic targets against coccidiosis, one of the most important avian diseases caused by the genus Eimeria, we identified and characterized Eimeria tenella aminopeptidase N1 (EtAPN1). Its inhibition by bestatin and amastatin, as well as its reactivation by divalent ions, is typical of zinc-dependent metalloproteases. EtAPN1 shared a similar sequence, three-dimensional structure, and substrate specificity and similar kinetic parameters with A-M1 from Plasmodium falciparum (PfA-M1), a validated target in the treatment of malaria. EtAPN1 is synthesized as a 120-kDa precursor and cleaved into 96-, 68-, and 38-kDa forms during sporulation. Further, immunolocalization assays revealed that, similar to PfA-M1, EtAPN1 is present during the intracellular life cycle stages in both the parasite cytoplasm and the parasite nucleus. The present results support the hypothesis of a conserved role between the two aminopeptidases, and we suggest that EtAPN1 might be a valuable target for anticoccidiosis drugs.",
author = "Simon Gras and Anna Byzia and Gilbert, {Florence B} and Sheena McGowan and Marcin Drag and Anne Silvestre and Alisson Niepceron and Fabien Lecaille and Gilles Lalmanach and Fabien Brossier",
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Gras, S, Byzia, A, Gilbert, FB, McGowan, S, Drag, M, Silvestre, A, Niepceron, A, Lecaille, F, Lalmanach, G & Brossier, F 2014, 'Aminopeptidase N1 (EtAPN1), an M1 metalloprotease of the apicomplexan parasite Eimeria tenella, participates in parasite development' Eukaryotic Cell, vol. 13, no. 7, pp. 884 - 895. https://doi.org/10.1128/EC.00062-14

Aminopeptidase N1 (EtAPN1), an M1 metalloprotease of the apicomplexan parasite Eimeria tenella, participates in parasite development. / Gras, Simon; Byzia, Anna; Gilbert, Florence B; McGowan, Sheena; Drag, Marcin; Silvestre, Anne; Niepceron, Alisson; Lecaille, Fabien; Lalmanach, Gilles; Brossier, Fabien.

In: Eukaryotic Cell, Vol. 13, No. 7, 2014, p. 884 - 895.

Research output: Contribution to journalArticleResearchpeer-review

TY - JOUR

T1 - Aminopeptidase N1 (EtAPN1), an M1 metalloprotease of the apicomplexan parasite Eimeria tenella, participates in parasite development

AU - Gras, Simon

AU - Byzia, Anna

AU - Gilbert, Florence B

AU - McGowan, Sheena

AU - Drag, Marcin

AU - Silvestre, Anne

AU - Niepceron, Alisson

AU - Lecaille, Fabien

AU - Lalmanach, Gilles

AU - Brossier, Fabien

PY - 2014

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N2 - Aminopeptidases N are metalloproteases of the M1 family that have been reported in numerous apicomplexan parasites, including Plasmodium, Toxoplasma, Cryptosporidium, and Eimeria. While investigating the potency of aminopeptidases as therapeutic targets against coccidiosis, one of the most important avian diseases caused by the genus Eimeria, we identified and characterized Eimeria tenella aminopeptidase N1 (EtAPN1). Its inhibition by bestatin and amastatin, as well as its reactivation by divalent ions, is typical of zinc-dependent metalloproteases. EtAPN1 shared a similar sequence, three-dimensional structure, and substrate specificity and similar kinetic parameters with A-M1 from Plasmodium falciparum (PfA-M1), a validated target in the treatment of malaria. EtAPN1 is synthesized as a 120-kDa precursor and cleaved into 96-, 68-, and 38-kDa forms during sporulation. Further, immunolocalization assays revealed that, similar to PfA-M1, EtAPN1 is present during the intracellular life cycle stages in both the parasite cytoplasm and the parasite nucleus. The present results support the hypothesis of a conserved role between the two aminopeptidases, and we suggest that EtAPN1 might be a valuable target for anticoccidiosis drugs.

AB - Aminopeptidases N are metalloproteases of the M1 family that have been reported in numerous apicomplexan parasites, including Plasmodium, Toxoplasma, Cryptosporidium, and Eimeria. While investigating the potency of aminopeptidases as therapeutic targets against coccidiosis, one of the most important avian diseases caused by the genus Eimeria, we identified and characterized Eimeria tenella aminopeptidase N1 (EtAPN1). Its inhibition by bestatin and amastatin, as well as its reactivation by divalent ions, is typical of zinc-dependent metalloproteases. EtAPN1 shared a similar sequence, three-dimensional structure, and substrate specificity and similar kinetic parameters with A-M1 from Plasmodium falciparum (PfA-M1), a validated target in the treatment of malaria. EtAPN1 is synthesized as a 120-kDa precursor and cleaved into 96-, 68-, and 38-kDa forms during sporulation. Further, immunolocalization assays revealed that, similar to PfA-M1, EtAPN1 is present during the intracellular life cycle stages in both the parasite cytoplasm and the parasite nucleus. The present results support the hypothesis of a conserved role between the two aminopeptidases, and we suggest that EtAPN1 might be a valuable target for anticoccidiosis drugs.

UR - http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4135734/pdf/zek884.pdf

U2 - 10.1128/EC.00062-14

DO - 10.1128/EC.00062-14

M3 - Article

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SP - 884

EP - 895

JO - mSphere

JF - mSphere

SN - 2379-5042

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