PDBsum entry 1tdh

Hydrolase

PDB id: 1tdh

Contents

Protein chain

284 a.a. *

Ligands

TRS

Waters ×307

* Residue conservation analysis

PDB id:

1tdh

Name:

Hydrolase

Title:

Crystal structure of human endonuclease viii-like 1 (neil1)

Structure:

Nei endonuclease viii-like 1. Chain: a. Engineered: yes

Source:

Homo sapiens. Human. Organism_taxid: 9606. Expressed in: escherichia coli. Expression_system_taxid: 562

Resolution:

2.10Å R-factor: 0.194 R-free: 0.231

Authors:

S.Doublie,V.Bandaru,J.P.Bond,S.S.Wallace

Key ref:

S.Doublié et al. (2004). The crystal structure of human endonuclease VIII-like 1 (NEIL1) reveals a zincless finger motif required for glycosylase activity. Proc Natl Acad Sci U S A, 101, 10284-10289. PubMed id: 15232006 DOI: 10.1073/pnas.0402051101

Date:

22-May-04 Release date: 20-Jul-04

Protein chain

Q96FI4  (NEIL1_HUMAN) -  Endonuclease 8-like 1 from Homo sapiens

Seq: 390 a.a.

Struc: 284 a.a.*

* PDB and UniProt seqs differ at 2 residue positions (black crosses)

Enzyme reactions

• Enzyme class 1: E.C.3.2.2.- - ?????
• Enzyme class 2: E.C.4.2.99.18 - DNA-(apurinic or apyrimidinic site) lyase.
• Reaction: 2'-deoxyribonucleotide-(2'-deoxyribose 5'-phosphate)- 2'-deoxyribonucleotide-DNA = a 3'-end 2'-deoxyribonucleotide-(2,3- dehydro-2,3-deoxyribose 5'-phosphate)-DNA + a 5'-end 5'-phospho- 2'-deoxyribonucleoside-DNA + H⁺

Note, where more than one E.C. class is given (as above), each may correspond to a different protein domain or, in the case of polyprotein precursors, to a different mature protein.

DOI no: 10.1073/pnas.0402051101

Proc Natl Acad Sci U S A 101:10284-10289 (2004)

PubMed id: 15232006

The crystal structure of human endonuclease VIII-like 1 (NEIL1) reveals a zincless finger motif required for glycosylase activity.

S.Doublié, V.Bandaru, J.P.Bond, S.S.Wallace.

ABSTRACT

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.

Selected figure(s)

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.

Figures were selected by an automated process.