Substrate Specificity of SAMHD1 Triphosphohydrolase Activity Is Controlled by Deoxyribonucleoside Triphosphates and Phosphorylation at Thr592
| Autor: | Jinwoo Ahn, Sunbok Jang, Xiaohong Zhou |
|---|---|
| Rok vydání: | 2016 |
| Předmět: |
Threonine
0301 basic medicine Deoxyribonucleosides Stereochemistry Dimer Deoxyribonucleotides Allosteric regulation Biochemistry Catalysis Article Substrate Specificity SAM Domain and HD Domain-Containing Protein 1 03 medical and health sciences chemistry.chemical_compound Tetramer heterocyclic compounds Phosphorylation Monomeric GTP-Binding Proteins chemistry.chemical_classification Chemistry Deoxyribonucleoside 030104 developmental biology Enzyme Sterile alpha motif SAMHD1 |
| Zdroj: | Biochemistry. 55:5635-5646 |
| ISSN: | 1520-4995 0006-2960 |
| Popis: | Sterile alpha motif (SAM) and Histidine-Aspartate (HD)-domain containing protein 1 (SAMHD1) is a triphosphohydrolase that converts deoxyribonucleoside triphosphates (dNTPs) into deoxyribonucleosides and triphosphates. SAMHD1 exists in multiple states. The monomer and apo- or GTP-bound dimer are catalytically inactive. Binding of dNTP at allosteric site 2 (AS2), adjacent to the GTP-binding, allosteric site 1 (AS1), induces formation of tetramer, the catalytically active form. We have developed an enzyme kinetic assay, tailored to control specific dNTP binding at each site, allowing us to determine the kinetic binding parameters of individual dNTPs at both the AS2 and catalytic site for all possible combinations of dNTP binding at both sites. Here, we show that the apparent Km values of dNTPs at AS2 vary, in order of dCTP |
| Databáze: | OpenAIRE |
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