6FK5

Structure of 3' phosphatase NExo (D146N) from Neisseria bound to DNA substrate in presence of magnesium ion

Summary for 6FK5

• Entry DOI: 10.2210/pdb6fk5/pdb
• Related: 6FK4
• Descriptor: NExo D146N, DNA (5'-D(P*CP*TP*AP*GP*CP*GP*AP*AP*GP*CP*TP*AP*GP*A)-3'), MAGNESIUM ION, ... (5 entities in total)
• Functional Keywords: 3' phosphatase, base excision dna repair, mg2+, dna binding protein
• Biological source: Neisseria meningitidis MC58; More
• Total number of polymer chains: 2
• Total formula weight: 35073.87

Authors

Silhan, J.,Zhao, Q.,Boura, E.,Thomson, H.,Foster, A.,Tang, C.M.,Freemont, P.S.,Baldwin, G.S. (deposition date: 2018-01-23, release date: 2018-10-31, Last modification date: 2024-01-17)

Primary citation

Silhan, J.,Zhao, Q.,Boura, E.,Thomson, H.,Forster, A.,Tang, C.M.,Freemont, P.S.,Baldwin, G.S.
Structural basis for recognition and repair of the 3'-phosphate by NExo, a base excision DNA repair nuclease from Neisseria meningitidis.
Nucleic Acids Res., 46:11980-11989, 2018

PubMed Abstract: NExo is an enzyme from Neisseria meningitidis that is specialized in the removal of the 3'-phosphate and other 3'-lesions, which are potential blocks for DNA repair. NExo is a highly active DNA 3'-phosphatase, and although it is from the class II AP family it lacks AP endonuclease activity. In contrast, the NExo homologue NApe, lacks 3'-phosphatase activity but is an efficient AP endonuclease. These enzymes act together to protect the meningococcus from DNA damage arising mainly from oxidative stress and spontaneous base loss. In this work, we present crystal structures of the specialized 3'-phosphatase NExo bound to DNA in the presence and absence of a 3'-phosphate lesion. We have outlined the reaction mechanism of NExo, and using point mutations we bring mechanistic insights into the specificity of the 3'-phosphatase activity of NExo. Our data provide further insight into the molecular origins of plasticity in substrate recognition for this class of enzymes. From this we hypothesize that these specialized enzymes lead to enhanced efficiency and accuracy of DNA repair and that this is important for the biological niche occupied by this bacterium.

PubMed: 30329088
DOI: 10.1093/nar/gky934

Experimental method

X-RAY DIFFRACTION (2.02 Å)