PMID: 8948483Nov 14, 1996Paper

Structural analysis of the catalytic site of AcCP-1, a cysteine proteinase secreted by the hookworm Ancylostoma caninum

Biochimica Et Biophysica Acta
R I BrinkworthS A Harrop

Abstract

Previously, we have reported that hookworms secrete cysteine proteinase activity that is capable of cleaving the cathepsin L-specific substrate Z-Phe-Arg-AMC. We have also reported the gene sequences of novel cathepsin B-like proteinases from hookworms, but have been unable to locate cathepsin L-like genes that could account for the presence of the cathepsin L activity in these parasites. Here we present an homology model for the secreted hookworm cysteine proteinase AcCP-1 based upon the crystal structure co-ordinates of human cathepsin B. The model predicts that substrate binding and specificity differs between AcCP-1 and cathepsin B, and demonstrates that AcCP-1 would preferentially cleave Phe-Arg over Arg-Arg. This thereby provides an explanation for our previous observations that the hookworm proteinase, while structurally cathepsin B-like, displays a cathepsin L-like substrate specificity.

References

Oct 1, 1986·Proceedings of the National Academy of Sciences of the United States of America·S J ChanD F Steiner
May 1, 1995·Molecular and Biochemical Parasitology·S A HarropP J Brindley
Sep 1, 1994·The American Journal of Tropical Medicine and Hygiene·A J DowdP J Brindley
Feb 15, 1993·The Biochemical Journal·N D Rawlings, A J Barrett
Apr 1, 1993·Proceedings of the National Academy of Sciences of the United States of America·K M KarrerM E DiTomas
Nov 30, 2000·Proceedings of the National Academy of Sciences of the United States of America·B E BernsteinS L Schreiber

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Citations

Jun 17, 2000·International Journal for Parasitology·R I BrinkworthP J Brindley
Mar 25, 2000·International Journal for Parasitology·M Blaxter
Jun 22, 2002·Molecular and Biochemical Parasitology·Collette Britton, Linda Murray
Jul 10, 1998·Molecular and Biochemical Parasitology·A LoukasR M Maizels
Mar 15, 2000·The International Journal of Biochemistry & Cell Biology·R I BrinkworthJ P Dalton
Jul 18, 2012·PLoS Neglected Tropical Diseases·Jon J VermeireConor R Caffrey
Dec 3, 1999·Immunological Reviews·P J HotezR A Koski
Mar 17, 2020·Parasites & Vectors·Asmaa M I AbuzeidGuoqing Li

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