A unique thioredoxin of the parasitic nematode Haemonchus contortus with glutaredoxin activity |
| |
| Authors: | Irene M Sotirchos Amanda L Hudson John Ellis Mary W Davey |
| |
| Institution: | 1. Institute for the Biotechnology of Infectious Diseases, University of Technology, Sydney, P.O. Box 123, Broadway NSW 2007, Australia;2. Department of Medical and Molecular Biosciences, University of Technology, Sydney, P.O. Box 123, Broadway NSW 2007, Australia;3. From the Department of Molecular Biology, College of Natural Sciences, Pusan National University, 2, Busandaehak-ro 63beon-gil, Geumjeong-gu, Busan 46241;5. the Pohang Accelerator Laboratory, Pohang University of Science and Technology, 80, Jigok-ro 127 beon-gil, Nam-gu, Pohang-si, Gyeongsangbuk-do 37673;4. the Department of Parasitology, School of Medicine, Pusan National University, 49, Busandaehak-ro, Mulgeum-eup, Yangsan-si, Gyeongsangnam-do 50612, Korea;1. Key Laboratory of Animal Parasitology of Ministry of Agriculture, Shanghai Veterinary Research Institute, Chinese Academy of Agricultural Sciences, Shanghai, 200241, China;2. Jiangsu Co-innovation Center for Prevention and Control of Important Animal Infectious Diseases and Zoonoses, Yangzhou, 225009, China;3. From the Institute of Infection and Global Health, University of Liverpool, Liverpool L3 5RF, UK;;4. Centre for Immunity, Infection & Evolution and Institute of Evolutionary Biology, University of Edinburgh, Edinburgh EH9 3JT, UK;;5. UMR 7245 MCAM CNRS, Muséum National d''Histoire Naturelle, 75231 Paris, France;;6. Division of Pathway Medicine, University of Edinburgh, Edinburgh EH9 3JT, UK;;1. Unidad de Biofísica (CSIC,UPV/EHU) and Departamento de Bioquímica, Universidad del País Vasco, Bilbao, Spain;2. OWL, Parque Científico y Tecnológico de Bizkaia, Bizkaia, Spain;3. Structural Biology Unit, Center for Cooperative Research in Biosciences, CICbiogune, Derio, Spain |
| |
| Abstract: | The dependency of parasites on the cellular redox systems has led to their investigation as novel drug targets. Defence against oxidative damage is through the thioredoxin and glutathione systems. The classic thioredoxin is identified by the active site Cys-Gly-Pro-Cys (CGPC). Here we describe the identification of a unique thioredoxin in the parasitic nematode, Haemonchus contortus. This thioredoxin-related protein, termed HcTrx5, has an arginine in its active site (Cys-Arg-Ser-Cys; CRSC) that is not found in any other organism. Recombinant HcTrx5 was able to reduce the disulfide bond in insulin, and be regenerated by mammalian thioredoxin reductase with a Km 2.19 ± 1.5 μM, similar to the classic thioredoxins. However, it was also able to reduce insulin when glutathione and glutathione reductase replaced the thioredoxin reductase. When coupled with H. contortus peroxiredoxin, HcTrx5 was active using either the thioredoxin reductase or the glutathione and glutathione reductase. HcTrx5 is expressed through the life cycle, with highest expression in the adult stage. The unique activity of this thioredoxin makes it a potential drug target for the control of this parasite. |
| |
| Keywords: | |
| 本文献已被 ScienceDirect 等数据库收录！ |
|
