PDBsum entry 2v1x

Hydrolase

PDB id: 2v1x

Contents

Protein chains

527 a.a. *

Ligands

ADP ×2

EDO ×2

Metals

_CL ×9

_MG ×2

_ZN ×2

Waters ×315

* Residue conservation analysis

PDB id:

2v1x

Name:

Hydrolase

Title:

Crystal structure of human recq-like DNA helicase

Structure:

Atp-dependent DNA helicase q1. Chain: a, b. Fragment: residues 49-616. Synonym: DNA-dependent atpase q1, recq DNA helicase. Engineered: yes

Source:

Homo sapiens. Human. Organism_taxid: 9606. Expressed in: escherichia coli. Expression_system_taxid: 469008. Expression_system_variant: r3-prare2.

Resolution:

2.00Å R-factor: 0.235 R-free: 0.278

Authors:

A.C.W.Pike,B.Shrestha,N.Burgess-Brown,O.King,E.Ugochukwu,S.Watt, A.Edwards,C.H.Arrowsmith,J.Weigelt,M.Sundstrom,O.Gileadi

Key ref:

A.C.Pike et al. (2009). Structure of the human RECQ1 helicase reveals a putative strand-separation pin. Proc Natl Acad Sci U S A, 106, 1039-1044. PubMed id: 19151156 DOI: 10.1073/pnas.0806908106

Date:

30-May-07 Release date: 03-Jul-07

Protein chains

P46063  (RECQ1_HUMAN) -  ATP-dependent DNA helicase Q1 from Homo sapiens

Seq: 649 a.a.

Struc: 527 a.a.

Enzyme reactions

• Enzyme class: E.C.5.6.2.4 - Dna 3'-5' helicase.

DOI no: 10.1073/pnas.0806908106

Proc Natl Acad Sci U S A 106:1039-1044 (2009)

PubMed id: 19151156

Structure of the human RECQ1 helicase reveals a putative strand-separation pin.

A.C.Pike, B.Shrestha, V.Popuri, N.Burgess-Brown, L.Muzzolini, S.Costantini, A.Vindigni, O.Gileadi.

ABSTRACT

RecQ-like helicases, which include 5 members in the human genome, are important in maintaining genome integrity. We present a crystal structure of a truncated form of the human RECQ1 protein with Mg-ADP. The truncated protein is active in DNA fork unwinding but lacks other activities of the full-length enzyme: disruption of Holliday junctions and DNA strand annealing. The structure of human RECQ1 resembles that of Escherichia coli RecQ, with some important differences. All structural domains are conserved, including the 2 RecA-like domains and the RecQ-specific zinc-binding and winged-helix (WH) domains. However, the WH domain is positioned at a different orientation from that of the E. coli enzyme. We identify a prominent beta-hairpin of the WH domain as essential for DNA strand separation, which may be analogous to DNA strand-separation features of other DNA helicases. This hairpin is significantly shorter in the E. coli enzyme and is not required for its helicase activity, suggesting that there are significant differences between the modes of action of RecQ family members.

Selected figure(s)

Figure 2.
Overview of RECQ1 structure. (A) Ribbon representation of a single RECQ1 molecule, viewed from 3 perpendicular orientations. The subdomains are identified by color: Core helicase domain D1, red; core helicase domain D2, blue; zinc motif (ZnD), yellow; helical hairpin (HH), orange; WH domain, green; and the β-hairpin in purple. ADP is shown in space-filling form. (B) E. coli RecQ, colored as in A. [PDB ID code 1OYY (30)] The molecule is viewed in the same orientation as the central view in A, using the D2 domain as a reference. (C) Side-by-side comparison of bacterial RecQ (Left) and human RECQ1 (Right). Arrows indicate the rotations of the various domains. The WH domain rotates 90° around the vertical (compare orientation of helix α1 marked by asterisk), the HH tilts up by 10°, and the D1 rotates away from D2.

Figure 3.
Details of the ADP and Zn-binding regions. (A) The nucleotide-binding pocket. Main chain and carbons are colored according the conserved motifs: motif 0 (yellow), motif I (magenta), motif II (light blue), motif V (gray). (B) Overlay of the Zn domains of RECQ1 (orange) and E. coli RecQ (gray). The yellow/black spheres indicate the zinc ion, which nearly overlap in the 2 structures. (C) Overlay of the WH domains of RECQ1 (red), WRN (blue), and E. coli RecQ (green). The β-hairpin forming one of the wings and the hydrophobic residues at the hairpin tip are highlighted.

Figures were selected by an automated process.