PDBsum entry 1tdh

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Hydrolase PDB id
Protein chain
284 a.a. *
Waters ×307
* Residue conservation analysis

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Key reference
Title The crystal structure of human endonuclease VIII-Like 1 (neil1) reveals a zincless finger motif required for glycosylase activity.
Authors S.Doublié, V.Bandaru, J.P.Bond, S.S.Wallace.
Ref. Proc Natl Acad Sci U S A, 2004, 101, 10284-10289. [DOI no: 10.1073/pnas.0402051101]
PubMed id 15232006
In prokaryotes, two DNA glycosylases recognize and excise oxidized pyrimidines: endonuclease III (Nth) and endonuclease VIII (Nei). The oxidized purine 8-oxoguanine, on the other hand, is recognized by Fpg (also known as MutM), a glycosylase that belongs to the same family as Nei. The recent availability of the human genome sequence allowed the identification of three human homologs of Escherichia coli Nei. We report here the crystal structure of a human Nei-like (NEIL) enzyme, NEIL1. The structure of NEIL1 exhibits the same overall fold as E. coli Nei, albeit with an unexpected twist. Sequence alignments had predicted that NEIL1 would lack a zinc finger, and it was therefore expected to use a different DNA-binding motif instead. Our structure revealed that, to the contrary, NEIL1 contains a structural motif composed of two antiparallel beta-strands that mimics the antiparallel beta-hairpin zinc finger found in other Fpg/Nei family members but lacks the loops that harbor the zinc-binding residues and, therefore, does not coordinate zinc. This "zincless finger" appears to be required for NEIL1 activity, because mutating a very highly conserved arginine within this motif greatly reduces the glycosylase activity of the enzyme.
Figure 3.
Fig. 3. Comparison of human NEIL1 with other Fpg/Nei DNA glycosylases. (A) Superposition of human NEIL1 (blue) with EcoNei (pink; PDB ID code 1K3W [PDB] ) (20) and TthFpg (green; PDB ID code 1EE8 [PDB] ) (21). The region encompassing the zinc-finger motif is boxed. An arrow points to the location of the F- 10 loop in Fpg. (B) Close-up of the zinc-finger motif. Shown are residues 230-262 for EcoNei, 231-266 for TthFpg, and 263-290 for human NEIL1. The asterisks indicate the position of the C of the conserved arginine.
Figure 4.
Fig. 4. NEIL1-DNA model. DNA from EcoNei complex (lesion-containing strand in green and complementary strand in pink) was superimposed onto human NEIL1 (blue). The zincless finger, H2TH, catalytic proline, and conserved arginine are highlighted in gold.
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