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Characterization of catalytic activity and structure of selenocysteine-containing hGSTZ1c-1c based on site-directed mutagenesis and computational analysis.
MedLine Citation:
PMID:  23299908     Owner:  NLM     Status:  Publisher    
Abstract/OtherAbstract:
Human glutathione transferase zeta 1c-1c (hGSTZ1c-1c) is one of the glutathione transferase isoenzymes and considered to be a protein scaffold to imitate glutathione peroxidase (GPX) owing to the natural binding site of glutathione (GSH). In this report, several residues near GSH were mutated to selenocysteine (Sec) or cysteine (Cys) residues and the impacts of the substitutions on different activities were discussed. Mutations of Ser-14 or/and Ser-15 to Cys or Sec residues resulted in dramatic loss of catalytic activity of hGSTZ1c-1c with chlorofluoroacetic acid as substrate, which indicated the importance of the hydroxyl groups in Ser-14 and Ser-15. And subsequent study by molecular modeling suggested that Ser-15 was probably involved in catalysis, while Ser-14 may play a crucial role in binding and orientation of GSH and possibly had a synergistic effect with Ser-15 in catalysis. On the contrary, the result of converting Cys-16 to Ser indicated its trivial role in catalysis. The investigations of the selenocysteine-containing hGSTZ1c-1c (seleno-hGSTZ1c-1c) and the mutant S17C implied that the substitutions of multi-Sec for Cys residues at position 16, 137, and 205 could lead to subtle change in the structure of the protein molecule and concomitant change in catalytic activity as a direct result. This finding provides overwhelming evidence that the protein scaffold containing fewer cysteines should be chosen for imitating GPX using cysteine auxotrophic strain system to avoid unexpected structural changes. © 2013 IUBMB Life, 2013.
Authors:
Yang Yu; Jian Song; Yang Song; Xiao Guo; Yiding Han; Jingyan Wei
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Publication Detail:
Type:  JOURNAL ARTICLE     Date:  2013-1-9
Journal Detail:
Title:  IUBMB life     Volume:  -     ISSN:  1521-6551     ISO Abbreviation:  IUBMB Life     Publication Date:  2013 Jan 
Date Detail:
Created Date:  2013-1-9     Completed Date:  -     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  100888706     Medline TA:  IUBMB Life     Country:  -    
Other Details:
Languages:  ENG     Pagination:  -     Citation Subset:  -    
Copyright Information:
Copyright © 2013 International Union of Biochemistry and Molecular Biology, Inc.
Affiliation:
College of Pharmaceutical Science, Jilin University, Changchun, China.
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