| 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 |
Related Documents
:
|
9010598 - Carbon monoxide binding to cytochrome p450bm-3: evidence for a substrate-dependent conf... 23060388 - Molecular mechanism of acrylamide neurotoxicity: lessons learned from organic chemistry. 23511748 - Spp1 at the crossroads of h3k4me3 regulation and meiotic recombination. 23416008 - 3d-qsar studies of 1,2-diaryl-1h-benzimidazole derivatives as jnk3 inhibitors with prot... 17007878 - The solution structure of a domain from the neisseria meningitidis lipoprotein pilp rev... 1445918 - Amino acid-specific adp-ribosylation: structural characterization and chemical differen... |
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. |
Export Citation:
|
APA/MLA Format Download EndNote Download BibTex |
| MeSH Terms | |
Descriptor/Qualifier:
|
|
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
Previous Document: Transoral robotic total laryngectomy.
Next Document: Interruption or deferral of antiretroviral therapy reduces markers of bone turnover compared with co...