5llq

Crystal structure of Sulfolobus solfataricus O6-methylguanine methyltransferase C119F variantCrystal structure of Sulfolobus solfataricus O6-methylguanine methyltransferase C119F variant

Structural highlights 5llq is a 2 chain structure with sequence from Saccharolobus solfataricus P2. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance. Method: X-ray diffraction, Resolution 2.7Å Ligands: Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT Function OGT_SACS2 Involved in the cellular defense against the biological effects of O6-methylguanine (O6-MeG) and O4-methylthymine (O4-MeT) in DNA. Repairs the methylated nucleobase in DNA by stoichiometrically transferring the methyl group to a cysteine residue in the enzyme. This is a suicide reaction: the enzyme is irreversibly inactivated.[HAMAP-Rule:MF_00772] Publication Abstract from PubMed BACKGROUND: Alkylated DNA-protein alkyltransferases (AGTs) are conserved proteins that repair alkylation damage in DNA by using a single-step mechanism leading to irreversible alkylation of the catalytic cysteine in the active site. Trans-alkylation induces inactivation and destabilization of the protein, both in vitro and in vivo, likely triggering conformational changes. A complete picture of structural rearrangements occurring during the reaction cycle is missing, despite considerable interest raised by the peculiarity of AGT reaction, and the contribution of a functional AGT in limiting the efficacy of chemotherapy with alkylating drugs. METHODS: As a model for AGTs we have used a thermostable ortholog from the archaeon Sulfolobus solfataricus (SsOGT), performing biochemical, structural, molecular dynamics and in silico analysis of ligand-free, DNA-bound and mutated versions of the protein. RESULTS: Conformational changes occurring during lesion recognition and after the reaction, allowed us to identify a novel interaction network contributing to SsOGT stability, which is perturbed when a bulky adduct between the catalytic cysteine and the alkyl group is formed, a mandatory step toward the permanent protein alkylation. CONCLUSIONS: Our data highlighted conformational changes and perturbation of intramolecular interaction occurring during lesion recognition and catalysis, confirming our previous hypothesis that coordination between the N- and C-terminal domains of SsOGT is important for protein activity and stability. GENERAL SIGNIFICANCE: A general model of structural rearrangements occurring during the reaction cycle of AGTs is proposed. If confirmed, this model might be a starting point to design strategies to modulate AGT activity in therapeutic settings. Interdomain interactions rearrangements control the reaction steps of a thermostable DNA alkyltransferase.,Morrone C, Miggiano R, Serpe M, Massarotti A, Valenti A, Del Monaco G, Rossi M, Rossi F, Rizzi M, Perugino G, Ciaramella M Biochim Biophys Acta. 2016 Oct 22;1861(2):86-96. doi:, 10.1016/j.bbagen.2016.10.020. PMID:27777086 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See Also DNA methyltransferase 3D structures

spinqualitylabelsall models 5llq, resolution 2.70Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image