5T3V

A Novel domain in human EXOG converts apoptotic endonuclease to DNA-repair enzyme

Summary for 5T3V

• Entry DOI: 10.2210/pdb5t3v/pdb
• Related: 5T40 5T4I 5T5C
• Descriptor: Nuclease EXOG, mitochondrial, MANGANESE (II) ION, SULFATE ION, ... (4 entities in total)
• Functional Keywords: mitochondria, exonuclease, dna-repair, complex, hydrolase
• Biological source: Homo sapiens (Human)
• Total number of polymer chains: 2
• Total formula weight: 72986.44

Authors

Szymanski, M.R.,Yin, W.Y. (deposition date: 2016-08-26, release date: 2017-05-17, Last modification date: 2024-10-30)

Primary citation

Szymanski, M.R.,Yu, W.,Gmyrek, A.M.,White, M.A.,Molineux, I.J.,Lee, J.C.,Yin, Y.W.
A domain in human EXOG converts apoptotic endonuclease to DNA-repair exonuclease.
Nat Commun, 8:14959-14959, 2017

PubMed Abstract: Human EXOG (hEXOG) is a 5'-exonuclease that is crucial for mitochondrial DNA repair; the enzyme belongs to a nonspecific nuclease family that includes the apoptotic endonuclease EndoG. Here we report biochemical and structural studies of hEXOG, including structures in its apo form and in a complex with DNA at 1.81 and 1.85 Å resolution, respectively. A Wing domain, absent in other ββα-Me members, suppresses endonuclease activity, but confers on hEXOG a strong 5'-dsDNA exonuclease activity that precisely excises a dinucleotide using an intrinsic 'tape-measure'. The symmetrical apo hEXOG homodimer becomes asymmetrical upon binding to DNA, providing a structural basis for how substrate DNA bound to one active site allosterically regulates the activity of the other. These properties of hEXOG suggest a pathway for mitochondrial BER that provides an optimal substrate for subsequent gap-filling synthesis by DNA polymerase γ.

PubMed: 28466855
DOI: 10.1038/ncomms14959

Experimental method

X-RAY DIFFRACTION (2.6 Å)