6U7T

MutY adenine glycosylase bound to DNA containing a transition state analog (1N) paired with d(8-oxo-G)

Replaces:  5DPKReplaces:  3FSQ

Summary for 6U7T

• Entry DOI: 10.2210/pdb6u7t/pdb
• Related: 6Q0C
• Descriptor: Adenine DNA glycosylase, DNA (5'-D(*AP*AP*GP*AP*CP*(8OG)P*TP*GP*GP*AP*C)-3'), DNA (5'-D(P*GP*TP*CP*CP*AP*(NR1)P*GP*TP*CP*T)-3'), ... (6 entities in total)
• Functional Keywords: protein-dna complex, dna repair, transition state analog, hydrolase-dna complex, hydrolase, hydrolase/dna
• Biological source: Geobacillus stearothermophilus; More
• Total number of polymer chains: 3
• Total formula weight: 48856.77

Authors

O'Shea Murray, V.L.,Cao, S.,Horvath, M.P.,David, S.S. (deposition date: 2019-09-03, release date: 2019-10-02, Last modification date: 2023-10-11)

Primary citation

Russelburg, L.P.,O'Shea Murray, V.L.,Demir, M.,Knutsen, K.R.,Sehgal, S.L.,Cao, S.,David, S.S.,Horvath, M.P.
Structural Basis for Finding OG Lesions and Avoiding Undamaged G by the DNA Glycosylase MutY.
Acs Chem.Biol., 15:93-102, 2020

PubMed Abstract: The adenine glycosylase MutY selectively initiates repair of OG:A lesions and, by comparison, avoids G:A mispairs. The ability to distinguish these closely related substrates relies on the C-terminal domain of MutY, which structurally resembles MutT. To understand the mechanism for substrate specificity, we crystallized MutY in complex with DNA containing G across from the high-affinity azaribose transition state analogue. Our structure shows that G is accommodated by the OG site and highlights the role of a serine residue in OG versus G discrimination. The functional significance of Ser308 and its neighboring residues was evaluated by mutational analysis, revealing the critical importance of a β loop in the C-terminal domain for mutation suppression in cells, and biochemical performance . This loop comprising residues Phe307, Ser308, and His309 ( sequence positions) is conserved in MutY but absent in MutT and other DNA repair enzymes and may therefore serve as a MutY-specific target exploitable by chemical biological probes.

PubMed: 31829624
DOI: 10.1021/acschembio.9b00639

Experimental method

X-RAY DIFFRACTION (2 Å)