Structure-function relationships governing activity and stability of a DNA alkylation damage repair thermostable protein
| Autor: | Anna Valenti, Samarpita Lahiri, Antonella Vettone, Riccardo Miggiano, Maria Ciaramella, Mario Serpe, Giuseppe Perugino, Mosè Rossi, Menico Rizzi, Franca Rossi |
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| Přispěvatelé: | Perugino, Giuseppe, Miggiano, Riccardo, Serpe, Mario, Vettone, Antonella, Valenti, Anna, Lahiri, Samarpita, Rossi, Franca, Rossi, Mosè, Rizzi, Menico, Ciaramella, Maria |
| Jazyk: | angličtina |
| Rok vydání: | 2015 |
| Předmět: |
Models
Molecular chemotherapy resistance HMG-box Alkylation DNA Repair DNA repair Alkyl and Aryl Transferase Archaeal Proteins Biology Genome Integrity Repair and Replication medicine.disease_cause chemistry.chemical_compound Structure-Activity Relationship Archaeal Protein Enzyme Stability Genetics medicine A-DNA chemistry.chemical_classification protein 3D structure Mutation DNA ligase Alkyl and Aryl Transferases DNA Sulfolobus solfataricu DNA Alkylation Biochemistry chemistry Sulfolobus solfataricus Alkyltransferase |
| Zdroj: | 'Nucleic Acids Research ', vol: 43, pages: 8801-8816 (2015) Nucleic Acids Research Europe PubMed Central Nucleic acids research (Online) 43 (2015): 8801–8816. doi:10.1093/nar/gkv774 info:cnr-pdr/source/autori:Perugino G, Miggiano R, Serpe M, Vettone A, Valenti A, Lahiri S, Rossi F, Rossi M, Rizzi M, Ciaramella M./titolo:Structure-function relationships governing activity and stability of a DNA alkylation damage repair thermostable protein./doi:10.1093%2Fnar%2Fgkv774/rivista:Nucleic acids research (Online)/anno:2015/pagina_da:8801/pagina_a:8816/intervallo_pagine:8801–8816/volume:43 |
| ISSN: | 0305-1048 |
| DOI: | 10.1093/nar/gkv774 |
| Popis: | Alkylated DNA-protein alkyltransferases repair alkylated DNA bases, which are among the most common DNA lesions, and are evolutionary conserved, from prokaryotes to higher eukaryotes. The human ortholog, hAGT, is involved in resistance to alkylating chemotherapy drugs. We report here on the alkylated DNA-protein alkyltransferase, SsOGT, from an archaeal species living at high temperature, a condition that enhances the harmful effect of DNA alkylation. The exceptionally high stability of SsOGT gave us the unique opportunity to perform structural and biochemical analysis of a protein of this class in its post-reaction form. This analysis, along with those performed on SsOGT in its ligand-free and DNA-bound forms, provides insights in the structure-function relationships of the protein before, during and after DNA repair, suggesting a molecular basis for DNA recognition, catalytic activity and protein post-reaction fate, and giving hints on the mechanism of alkylation-induced inactivation of this class of proteins. |
| Databáze: | OpenAIRE |
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