3SZQ

Structure of an S. pombe APTX/DNA/AMP/Zn complex

Summary for 3SZQ

• Entry DOI: 10.2210/pdb3szq/pdb
• Descriptor: Aprataxin-like protein, 5'-D(*CP*CP*CP*TP*G)-3', 5'-D(*TP*AP*TP*CP*GP*GP*AP*AP*TP*CP*AP*GP*GP*G)-3', ... (7 entities in total)
• Functional Keywords: histidine triad (hit), c2he zinc finger, dna repair, hydrolase-dna complex, hydrolase/dna
• Biological source: Schizosaccharomyces pombe (Fission yeast)
• Cellular location: Nucleus : O74859
• Total number of polymer chains: 3
• Total formula weight: 30267.16

Authors

Tumbale, P.,Krahn, J.,Williams, R.S. (deposition date: 2011-07-19, release date: 2011-10-12, Last modification date: 2024-02-28)

Primary citation

Tumbale, P.,Appel, C.D.,Kraehenbuehl, R.,Robertson, P.D.,Williams, J.S.,Krahn, J.,Ahel, I.,Williams, R.S.
Structure of an aprataxin-DNA complex with insights into AOA1 neurodegenerative disease.
Nat.Struct.Mol.Biol., 18:1189-1195, 2011

PubMed Abstract: DNA ligases finalize DNA replication and repair through DNA nick-sealing reactions that can abort to generate cytotoxic 5'-adenylation DNA damage. Aprataxin (Aptx) catalyzes direct reversal of 5'-adenylate adducts to protect genome integrity. Here the structure of a Schizosaccharomyces pombe Aptx-DNA-AMP-Zn(2+) complex reveals active site and DNA interaction clefts formed by fusing a histidine triad (HIT) nucleotide hydrolase with a DNA minor groove-binding C(2)HE zinc finger (Znf). An Aptx helical 'wedge' interrogates the base stack for sensing DNA ends or DNA nicks. The HIT-Znf, the wedge and an '[F/Y]PK' pivot motif cooperate to distort terminal DNA base-pairing and direct 5'-adenylate into the active site pocket. Structural and mutational data support a wedge-pivot-cut HIT-Znf catalytic mechanism for 5'-adenylate adduct recognition and removal and suggest that mutations affecting protein folding, the active site pocket and the pivot motif underlie Aptx dysfunction in the neurodegenerative disorder ataxia with oculomotor apraxia 1 (AOA1).

PubMed: 21984210
DOI: 10.1038/nsmb.2146

Experimental method

X-RAY DIFFRACTION (2.353 Å)