4ZYD

Crystal structure of Sulfolobus solfataricus O6-methylguanine methyltransferase in complex with modified DNA

Summary for 4ZYD

• Entry DOI: 10.2210/pdb4zyd/pdb
• Descriptor: Methylated-DNA--protein-cysteine methyltransferase, DNA (5'-D(*GP*CP*CP*AP*TP*GP*(6OG)P*CP*TP*AP*GP*TP*A)-3'), DNA (5'-D(*TP*AP*CP*TP*AP*GP*CP*CP*AP*TP*GP*GP*C)-3'), ... (4 entities in total)
• Functional Keywords: transferase, extremophiles, dna repair, alkylated dna-protein alkyltransferase, protein-dna complex, cell cycle
• Biological source: Sulfolobus solfataricus; More
• Cellular location: Cytoplasm : Q97VW7
• Total number of polymer chains: 3
• Total formula weight: 24985.22

Authors

Miggiano, R.,Rossi, F.,Rizzi, M. (deposition date: 2015-05-21, release date: 2015-08-12, Last modification date: 2024-01-10)

Primary citation

Perugino, G.,Miggiano, R.,Serpe, M.,Vettone, A.,Valenti, A.,Lahiri, S.,Rossi, F.,Rossi, M.,Rizzi, M.,Ciaramella, M.
Structure-function relationships governing activity and stability of a DNA alkylation damage repair thermostable protein.
Nucleic Acids Res., 43:8801-8816, 2015

PubMed Abstract: 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.

PubMed: 26227971
DOI: 10.1093/nar/gkv774

Experimental method

X-RAY DIFFRACTION (2.682 Å)