PDBsum entry 2e1e

Hydrolase

PDB id: 2e1e

Contents

Protein chain

94 a.a. *

Metals

_CL

Waters ×29

* Residue conservation analysis

PDB id:

2e1e

Name:

Hydrolase

Title:

Crystal structure of the hrdc domain of human werner syndrome protein, wrn

Structure:

Werner syndrome atp-dependent helicase. Chain: a. Fragment: hrdc domain. Engineered: yes

Source:

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

Biol. unit:

Monomer (from PQS)

Resolution:

2.30Å R-factor: 0.253 R-free: 0.279

Authors:

K.Kitano,N.Yoshihara,T.Hakoshima

Key ref:

K.Kitano et al. (2007). Crystal structure of the HRDC domain of human Werner syndrome protein, WRN. J Biol Chem, 282, 2717-2728. PubMed id: 17148451 DOI: 10.1074/jbc.M610142200

Date:

25-Oct-06 Release date: 12-Dec-06

Protein chain

Q14191  (WRN_HUMAN) -  Bifunctional 3'-5' exonuclease/ATP-dependent helicase WRN from Homo sapiens

Seq: 1432 a.a.

Struc: 94 a.a.

Enzyme reactions

• Enzyme class 1: E.C.3.1.-.-
• Enzyme class 2: E.C.3.6.4.12 - Dna helicase.
• Reaction: ATP + H2O = ADP + phosphate + 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.

Molecule diagrams generated from .mol files obtained from the KEGG ftp site

reference

DOI no: 10.1074/jbc.M610142200

J Biol Chem 282:2717-2728 (2007)

PubMed id: 17148451

Crystal structure of the HRDC domain of human Werner syndrome protein, WRN.

K.Kitano, N.Yoshihara, T.Hakoshima.

ABSTRACT

Werner syndrome is a human premature aging disorder characterized by chromosomal instability. The disease is caused by the functional loss of WRN, a member of the RecQ-helicase family that plays an important role in DNA metabolic pathways. WRN contains four structurally folded domains comprising an exonuclease, a helicase, a winged-helix, and a helicase-and-ribonuclease D/C-terminal (HRDC) domain. In contrast to the accumulated knowledge pertaining to the biochemical functions of the three N-terminal domains, the function of C-terminal HRDC remains unknown. In this study, the crystal structure of the human WRN HRDC domain has been determined. The domain forms a bundle of alpha-helices similar to those of Saccharomyces cerevisiae Sgs1 and Escherichia coli RecQ. Surprisingly, the extra ten residues at each of the N and C termini of the domain were found to participate in the domain architecture by forming an extended portion of the first helix alpha1, and a novel looping motif that traverses straight along the domain surface, respectively. The motifs combine to increase the domain surface of WRN HRDC, which is larger than that of Sgs1 and E. coli.In WRN HRDC, neither of the proposed DNA-binding surfaces in Sgs1 or E. coli is conserved, and the domain was shown to lack DNA-binding ability in vitro. Moreover, the domain was shown to be thermostable and resistant to protease digestion, implying independent domain evolution in WRN. Coupled with the unique long linker region in WRN, the WRN HRDC may be adapted to play a distinct function in WRN that involves protein-protein interactions.

Selected figure(s)

Figure 2.
FIGURE 2. Crystal structure of the human WRN HRDC domain. A, front view (left) and top view (right) of WRN HRDC in a ribbon model. Secondary structure elements are labeled, and dimensions of the molecule are indicated. Molecular surface of the domain is shown in transparent gray (conventional HRDC core) and red (N- and C-terminal extensions unique to WRN). B, superimposition of WRN HRDC (green) with Sgs1 (19) (pink) and E. coli (20) (yellow) HRDCs. The orientation is the same as in A. The N and C termini of each molecule are labeled. Superimposition was performed using LSQMAN (56).

Figure 3.
FIGURE 3. C-terminal extended loop packed to the HRDC core. A,a stick model represents carbon atoms of the nine C-terminal residues (1227–1235, labeled with one-letter codes) shown in cyan, whereas the other part of the domain including N-terminal extended helix 1 is in green. The composite-omit density map (25) for the C-terminal residues is shown at the contour level of 1 . The orientation is similar to that in Fig. 2A (top view). B, schematic representation depicting the interactions between the C-terminal extended loop (cyan) and HRDC core, including helix 1(green). Hydrogen bonds are shown as dashed lines with distances (Å) shown. Two hydrophobic pockets on the HRDC core (pocket-1 formed by side chains from Thr^1152, Phe^1222, Cys^1223, and Asn^1226, and pocket-2 formed by Met^1190, Pro^1192, Asn^1197, Ile^1201, and Arg^1200) that are important for the binding of C-terminal residues are indicated.

The above figures are reprinted by permission from the ASBMB: J Biol Chem (2007, 282, 2717-2728) copyright 2007.

Figures were selected by the author.