PDBsum entry: 1y97

Hydrolase

PDB id: 1y97

Contents

Protein chains

214 a.a. *

Waters ×77

* Residue conservation analysis

PDB id:

1y97

Name:

Hydrolase

Title:

The human trex2 3' exonuclease structure suggests a mechanism for efficient non-processive DNA catalysis

Structure:

Three prime repair exonuclease 2. Chain: a, b. Fragment: trex2 exonuclease. Synonym: 3'-5' exonuclease trex2. Engineered: yes

Source:

Homo sapiens. Human. Organism_taxid: 9606. Gene: trex2. Expressed in: escherichia coli. Expression_system_taxid: 562

Biol. unit:

Dimer (from PQS)

Resolution:

2.50Å R-factor: 0.205 R-free: 0.261

Authors:

F.W.Perrino,S.Harvey,S.Mcmillin,T.Hollis

Key ref:

F.W.Perrino et al. (2005). The human TREX2 3' -> 5'-exonuclease structure suggests a mechanism for efficient nonprocessive DNA catalysis. J Biol Chem, 280, 15212-15218. PubMed id: 15661738 DOI: 10.1074/jbc.M500108200

Date:

14-Dec-04 Release date: 25-Jan-05

Protein chains

Q9BQ50  (TREX2_HUMAN) -  Three prime repair exonuclease 2

Seq: 279 a.a.

Struc: 214 a.a.*

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

Enzyme reactions

• Enzyme class: E.C.3.1.11.2 - Exodeoxyribonuclease Iii.
• Reaction: Degradation of double-stranded DNA. It acts progressively in a 3'- to 5'-direction, releasing nucleoside 5'-phosphates.

 Gene Ontology (GO) functional annotation 

• Cellular component: intracellular (1 term)
• Biochemical function: nucleic acid binding (2 terms)

DOI no: 10.1074/jbc.M500108200

J Biol Chem 280:15212-15218 (2005)

PubMed id: 15661738

The human TREX2 3' -> 5'-exonuclease structure suggests a mechanism for efficient nonprocessive DNA catalysis.

F.W.Perrino, S.Harvey, S.McMillin, T.Hollis.

ABSTRACT

The 3' --> 5'-exonucleases process DNA ends in many DNA repair pathways of human cells. Determination of the human TREX2 structure is the first of a dimeric 3'-deoxyribonuclease and indicates how this highly efficient nonprocessive enzyme removes nucleotides at DNA 3' termini. Symmetry in the TREX2 dimer positions the active sites at opposite outer edges providing open access for the DNA. Adjacent to each active site is a flexible region containing three arginines positioned appropriately to bind DNA and to control its entry into the active site. Mutation of these three arginines to alanines reduces the DNA binding capacity by approximately 100-fold with no effect on catalysis. The human TREX2 catalytic residues overlay with the bacterial DnaQ family of 3'-exonucleases confirming the structural conservation of the catalytic sites despite limited sequence identity, and mutations of these residues decrease the still measurable activity by approximately 10(5)-fold, confirming their catalytic role.

Selected figure(s)

Figure 1.
FIG. 1. The TREX2 protein forms a dimer. A, the structure of TREX2 shows a five-stranded, twisted, antiparallel -sheet surrounded by 9 helices. The protein dimerizes about a 2-fold axis perpendicular to the -strands to form an extended -sheet that extends across the dimer (monomers shown in red and blue). B, TREX2 dimerization positions the active sites (yellow circles) of each monomer on opposite edges of the same face of the dimer. The TREX2 protein possesses little positive charge except in the region adjacent to the active sites. The active sites themselves appear to have an overall negative charge because of the presence of the four conserved acidic residues required for magnesium ion coordination (metal ions not present in structure). All ribbon diagrams and electron density shown in Fig. 2 were made with the program SETOR (35) and protein electrostatic potential surfaces made with the program GRASP (39).

Figure 5.
FIG. 5. Model of nucleotide binding to TREX2 (stereo figure). The model was constructed by a superposition of the structure of the exonuclease domain of DNA polymerase I in complex with phosphorothioate containing DNA (PDB code 1KSP [PDB] ) onto the TREX2 structure (green). The model shows good positioning of the DNA (gold) relative to the conserved catalytic residues (red) with no major steric clashes. Arg152, which is structurally conserved in the exoI and structures, is properly positioned adjacent to the active site to interact with the phosphodiester backbone of the substrate DNA.

The above figures are reprinted by permission from the ASBMB: J Biol Chem (2005, 280, 15212-15218) copyright 2005.

Figures were selected by an automated process.