PDBsum entry 6q0c

Hydrolase/DNA

PDB id: 6q0c

Contents

Protein chain

349 a.a.

DNA/RNA

Ligands

SF4

EDO

Metals

_CA

Waters ×71

PDB id:

6q0c

Name:

Hydrolase/DNA

Title:

Muty adenine glycosylase bound to DNA containing a transition state analog (1n) paired with undamaged dg

Structure:

A/g-specific adenine glycosylase. Chain: a. Engineered: yes. DNA (5'-d( Ap Ap Gp Ap Cp Gp Tp Gp Gp Ap C)-3'). Chain: b. Engineered: yes. DNA (5'-d(p Gp Tp Cp Cp Ap (Nr1)p Gp Tp Cp T)-3'). Chain: c. Engineered: yes

Source:

Geobacillus stearothermophilus. Organism_taxid: 1422. Gene: muty. Expressed in: escherichia coli bl21(de3). Expression_system_taxid: 469008. Synthetic: yes. Synthetic construct. Organism_taxid: 32630. Organism_taxid: 32630

Resolution:

2.00Å R-factor: 0.249 R-free: 0.271

Authors:

V.L.O'Shea Murray,L.P.Russelburg,M.P.Horvath,S.S.David

Key ref:

L.P.Russelburg et al. (2020). Structural Basis for Finding OG Lesions and Avoiding Undamaged G by the DNA Glycosylase MutY. ACS Chem Biol, 15, 93. PubMed id: 31829624 DOI: 10.1021/acschembio.9b00639

Date:

01-Aug-19 Release date: 28-Aug-19

Supersedes:

3fsp

Protein chain

P83847  (MUTY_GEOSE) -  Adenine DNA glycosylase from Geobacillus stearothermophilus

Seq: 366 a.a.

Struc: 349 a.a.

DNA/RNA chains

A-A-G-A-C-G-T-G-G-A-C 11 bases

G-T-C-C-A-NR1-G-T-C-T 10 bases

Enzyme reactions

• Enzyme class: E.C.3.2.2.31 - adenine glycosylase.

DOI no: 10.1021/acschembio.9b00639

ACS Chem Biol 15:93 (2020)

PubMed id: 31829624

Structural Basis for Finding OG Lesions and Avoiding Undamaged G by the DNA Glycosylase MutY.

L.P.Russelburg, V.L.O'Shea Murray, M.Demir, K.R.Knutsen, S.L.Sehgal, S.Cao, S.S.David, M.P.Horvath.

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 in vitro. This loop comprising residues Phe307, Ser308, and His309 (Geobacillus stearothermophilus 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.