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WRN exonuclease

spinqualitylabelsall models PDB ID 2fbv Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image
2fbv, resolution 2.40Å ()
Ligands:
Gene:	WRN, RECQ3, RECQL2 (Homo sapiens)
Related:	2fbt, 2fbx, 2fby, 2fc0
Structural annotation: Resources: InterPro : Ipr004589, Ipr014021, Ipr014001, Ipr002464, Ipr001650, Ipr002121, Ipr002562, Ipr012337, Ipr011545 Pfam : PF01612 UniProt : Q14191
Functional annotation: Cellular component: nucleus intracellular Biological process: regulation of growth rate aging DNA recombination telomere maintenance Molecular function: 3'-5' exonuclease activity hydrolase activity DNA binding helicase activity nucleotide binding ATP binding DNA helicase activity nucleic acid binding protein binding ATP-dependent helicase activity
Evolutionary conservation: Toggle Conservation Colors: Rows = identical sequences: Further Information: Caveats, Explanation, Complete Results at ConSurfDB
Resources:	FirstGlance, OCA, RCSB, PDBsum
Coordinates:	save as pdb, mmCIF, xml

Introduction

Werner (WRN) protein is a member of the human RecQDNA helicases. This enzyme has a helicases function (unwinding double-stranded DNA helix in the 3'-5' direction) and a exonuclease activity (degrading), which allows for deletion of mutation and proofreading. The WRN has a functional exonuclease domain located on the N-terminus. WRN protein protects human from cancer; as well as, premature aging.

Structure

The WRN protein is built from several individual WRN copies. The exonuclease region of the protein is located at the N-terminal end with 171 amino acids. They form a hexamer around the end of the strand when exposed to double strand DNA, which is essential to DNA repair of the WRN.

The HRDC domain has 80 amino acids at the C-terminal end. There are five helicases connected by turns and hydrophobic loops. These hydrobopic loops are needed for for packing the domain into a bundle. This domain contributes in the interaction with the double stranded DNA.

The catalysis the exonuclease activity by having the Mn²⁺ or Mg²⁺ complex. Mg²⁺ are more commonly cofactors in the cell; however, Mn²⁺ supports higher catalytic activity. This active site contains Glu₈₄, Tyr₂₁₂, Ala₁₈₈, Glu₁₉₂, Asp₂₁₆, Asp₈₂, Tyr₅₄ and Asp₁₄₃.^[1] When bond to the active site the two metals have a distance of 3.7 Å separating them when bound to the active site.^[1] The inner Mn²⁺ is directly coordinated with Asp₈₂, Glu₈₄ and Asp₂₁₆.^[1] The outer metal ion binds with a ligatures side chain Asp₈₂ to form the bridge between the two metal ions.^[1] Asp₁₄₃ interacts indirectly with the outer metal ion by two water molecules. ^[1] WRN exonuclease functions on different structures of a DNA substrate.^[2] The metal ions Mn²⁺ are needed to stimulate the exonuclease active of the WRN. However, WRN exonuclease can be blocked by oxidatively induced base lesion (damaged by disease tissue).^[3]