8uuc

Crystal structure of a bacterial clusterless MutYX bound to an Abasic site analog (THF) opposite d(8-oxo-G)

spinqualitylabelsall models 8uuc, resolution 1.55Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 8uuc is a 3 chain structure with sequence from Eggerthella sp. YY7918 and Synthetic construct. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance. Method: X-ray diffraction, Resolution 1.55Å Ligands: 3DR, 8OG, CL, EDO, MG, NA, PO4 Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT Function F7V0V1_EEGSY Publication Abstract from PubMed The [4Fe-4S] cluster is an important cofactor of the base excision repair (BER) adenine DNA glycosylase MutY to prevent mutations associated with 8-oxoguanine (OG). Several MutYs lacking the [4Fe-4S] cofactor have been identified. Phylogenetic analysis shows that clusterless MutYs are distributed in two clades suggesting cofactor loss in two independent evolutionary events. Herein, we determined the first crystal structure of a clusterless MutY complexed with DNA. On the basis of the dramatic structural divergence from canonical MutYs, we refer to this as representative of a clusterless MutY subgroup "MutYX". Interestingly, MutYX compensates for the missing [4Fe-4S] cofactor to maintain positioning of catalytic residues by expanding a pre-existing alpha-helix and acquisition of the new alpha-helix. Surprisingly, MutYX also acquired a new C-terminal domain that uniquely recognizes OG using residue Gln201 and Arg209. Adenine glycosylase assays and binding affinity measurements indicate that Arg209 is the primary residue responsible to specificity for OG:A lesions, while Gln201 bridges OG and Arg209. Surprisingly, replacement of Arg209 and Gln201 with Ala increases activity toward G:A mismatches. The MutYX structure serves as an example of devolution, capturing structural features required to retain function in the absence of a metal cofactor considered indispensable. Crystal structure of MutYX: A novel clusterless adenine DNA glycosylase with a distinct C-terminal domain and 8-Oxoguanine recognition sphere.,Trasvina-Arenas CH, Hashemian M, Malek M, Merrill S, Fisher AJ, David SS bioRxiv [Preprint]. 2025 Jan 3:2025.01.03.631205. doi: 10.1101/2025.01.03.631205. PMID:39803464 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

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