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Tuned by metals: the TET peptidase activity is controlled by 3 metal binding sites
- Source :
- 'Scientific Reports ', vol: 6, pages: 20876-1-20876-13 (2016), Scientific Reports, Scientific Reports, Nature Publishing Group, 2016, 6, ⟨10.1038/srep20876⟩, Scientific Reports, 2016, 6, ⟨10.1038/srep20876⟩
- Publication Year :
- 2016
- Publisher :
- Nature Publishing Group, 2016.
-
Abstract
- TET aminopeptidases are dodecameric particles shared in the three life domains involved in various biological processes, from carbon source provider in archaea to eye-pressure regulation in humans. Each subunit contains a dinuclear metal site (M1 and M2) responsible for the enzyme catalytic activity. However, the role of each metal ion is still uncharacterized. Noteworthy, while mesophilic TETs are activated by Mn2+, hyperthermophilic TETs prefers Co2+. Here, by means of anomalous x-ray crystallography and enzyme kinetics measurements of the TET3 aminopeptidase from the hyperthermophilic organism Pyrococcus furiosus (PfTET3), we show that M2 hosts the catalytic activity of the enzyme, while M1 stabilizes the TET3 quaternary structure and controls the active site flexibility in a temperature dependent manner. A new third metal site (M3) was found in the substrate binding pocket, modulating the PfTET3 substrate preferences. These data show that TET activity is tuned by the molecular interplay among three metal sites.
- Subjects :
- 0301 basic medicine
Models, Molecular
Stereochemistry
Protein Conformation
Molecular Conformation
Crystallography, X-Ray
Aminopeptidases
Catalysis
Article
03 medical and health sciences
Enzyme activator
Catalytic Domain
Hydrolase
Enzyme kinetics
Binding site
Multidisciplinary
Binding Sites
biology
[SDV.BBM.BS]Life Sciences [q-bio]/Biochemistry, Molecular Biology/Structural Biology [q-bio.BM]
Chemistry
Temperature
Active site
Substrate (chemistry)
biology.organism_classification
Enzyme Activation
030104 developmental biology
Biochemistry
Metals
biology.protein
Pyrococcus furiosus
Protein quaternary structure
Protein Multimerization
Copper
Protein Binding
Subjects
Details
- Language :
- English
- ISSN :
- 20452322
- Database :
- OpenAIRE
- Journal :
- Scientific Reports
- Accession number :
- edsair.doi.dedup.....c60d40f7484d2b0c6f50218795678841
- Full Text :
- https://doi.org/10.1038/srep20876