title: Advanced enzymology, expression profile and immune response of Clonorchis sinensis hexokinase show its application potential for prevention and control of clonorchiasis.
abstract: BACKGROUND
  Approximately 35 million people are infected with Clonorchis sinensis (C. sinensis) globally, of whom 15 million are in China. Glycolytic enzymes are recognized as crucial molecules for trematode survival and have been targeted for vaccine and drug development. Hexokinase of C. sinensis (CsHK), as the first key regulatory enzyme of the glycolytic pathway, was investigated in the current study.
  
  
  RESULTS
  There were differences in spatial structure and affinities for hexoses and phosphate donors between CsHK and HKs from humans or rats, the definitive hosts of C. sinensis. Effectors (AMP, PEP, and citrate) and a small molecular inhibitor regulated the enzymatic activity of rCsHK, and various allosteric systems were detected. CsHK was distributed in the worm extensively as well as in liver tissue and serum from C. sinensis infected rats. Furthermore, high-level specific IgG1 and IgG2a were induced in rats by immunization with rCsHK. The enzymatic activity of CsHK was suppressed by the antibody in vitro. Additionally, the survival of C. sinensis was inhibited by the antibody in vivo and in vitro.
  
  
  CONCLUSIONS
  Due to differences in putative spatial structure and enzymology between CsHK and HK from the host, its extensive distribution in adult worms, and its expression profile as a component of excretory/secretory products, together with its good immunogenicity and immunoreactivity, as a key glycolytic enzyme, CsHK shows potential as a vaccine and as a promising drug target for Clonorchiasis.
authors: Department of Parasitology, Zhongshan School of Medicine, Sun Yat-sen University, Guangzhou, Guangdong, China; Key Laboratory for Tropical Disease Control, Sun Yat-sen University, Ministry of Education, Guangzhou, Guangdong, China.
authors: Tingjin
authors: T
authors: Chen
authors: Department of Parasitology, Zhongshan School of Medicine, Sun Yat-sen University, Guangzhou, Guangdong, China; Key Laboratory for Tropical Disease Control, Sun Yat-sen University, Ministry of Education, Guangzhou, Guangdong, China.
authors: Jinyun
authors: J
authors: Yu
authors: Department of Parasitology, Zhongshan School of Medicine, Sun Yat-sen University, Guangzhou, Guangdong, China; Key Laboratory for Tropical Disease Control, Sun Yat-sen University, Ministry of Education, Guangzhou, Guangdong, China.
authors: Zeli
authors: Z
authors: Tang
authors: Department of Parasitology, Zhongshan School of Medicine, Sun Yat-sen University, Guangzhou, Guangdong, China; Key Laboratory for Tropical Disease Control, Sun Yat-sen University, Ministry of Education, Guangzhou, Guangdong, China.
authors: Zhizhi
authors: Z
authors: Xie
authors: Department of Parasitology, Zhongshan School of Medicine, Sun Yat-sen University, Guangzhou, Guangdong, China; Key Laboratory for Tropical Disease Control, Sun Yat-sen University, Ministry of Education, Guangzhou, Guangdong, China.
authors: Zhipeng
authors: Z
authors: Lin
authors: Department of Parasitology, Zhongshan School of Medicine, Sun Yat-sen University, Guangzhou, Guangdong, China; Key Laboratory for Tropical Disease Control, Sun Yat-sen University, Ministry of Education, Guangzhou, Guangdong, China.
authors: Hengchang
authors: H
authors: Sun
authors: Department of Parasitology, Zhongshan School of Medicine, Sun Yat-sen University, Guangzhou, Guangdong, China; Key Laboratory for Tropical Disease Control, Sun Yat-sen University, Ministry of Education, Guangzhou, Guangdong, China.
authors: Shuo
authors: S
authors: Wan
authors: Department of Parasitology, Zhongshan School of Medicine, Sun Yat-sen University, Guangzhou, Guangdong, China; Key Laboratory for Tropical Disease Control, Sun Yat-sen University, Ministry of Education, Guangzhou, Guangdong, China.
authors: Xuerong
authors: X
authors: Li
authors: Department of Parasitology, Zhongshan School of Medicine, Sun Yat-sen University, Guangzhou, Guangdong, China; Key Laboratory for Tropical Disease Control, Sun Yat-sen University, Ministry of Education, Guangzhou, Guangdong, China.
authors: Yan
authors: Y
authors: Huang
authors: Department of Parasitology, Zhongshan School of Medicine, Sun Yat-sen University, Guangzhou, Guangdong, China; Key Laboratory for Tropical Disease Control, Sun Yat-sen University, Ministry of Education, Guangzhou, Guangdong, China.
authors: Xinbing
authors: X
authors: Yu
authors: Department of Parasitology, Zhongshan School of Medicine, Sun Yat-sen University, Guangzhou, Guangdong, China; Key Laboratory for Tropical Disease Control, Sun Yat-sen University, Ministry of Education, Guangzhou, Guangdong, China.
authors: Jin
authors: J
authors: Xu
mesh_terms: D000494:Allosteric Regulation / Q000502:physiology; D000818:Animals; D003003:Clonorchiasis / Q000201:enzymology / Q000517:prevention & control*; D003004:Clonorchis sinensis / Q000201:enzymology* / Q000276:immunology*; D006593:Hexokinase / Q000097:blood / Q000378:metabolism* / Q000627:therapeutic use; D006801:Humans; D007074:Immunoglobulin G / Q000097:blood; D008099:Liver / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D013045:Species Specificity; D014612:Vaccines / Q000276:immunology
chemical_list: D007074:Immunoglobulin G; D014612:Vaccines; D006593:Hexokinase