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PMID: 14517231 Published · ppublish English Journal Article Research Support, Non-U.S. Gov't Research Support, U.S. Gov't, P.H.S.

High-resolution structure of the E.coli RecQ helicase catalytic core.

The EMBO journal ·Vol. 22 ·No. 19 ·2003-10-01 ·Pages 4910-21

Bernstein DA, Zittel MC, Keck JL

Abstract

RecQ family helicases catalyze critical genome maintenance reactions in bacterial and eukaryotic cells, playing key roles in several DNA metabolic processes. Mutations in recQ genes are linked to genome instability and human disease. To define the physical basis of RecQ enzyme function, we have determined a 1.8 A resolution crystal structure of the catalytic core of Escherichia coli RecQ in its unbound form and a 2.5 A resolution structure of the core bound to the ATP analog ATPgammaS. The RecQ core comprises four conserved subdomains; two of these combine to form its helicase region, while the others form unexpected Zn(2+)-binding and winged-helix motifs. The structures reveal the molecular basis of missense mutations that cause Bloom's syndrome, a human RecQ-associated disease. Finally, based on findings from the structures, we propose a mechanism for RecQ activity that could explain its functional coordination with topoisomerase III.

MeSH Terms
Adenosine Triphosphatases/chemistry,genetics Amino Acid Sequence Catalytic Domain DNA Helicases/chemistry,genetics Escherichia coli/enzymology,genetics Molecular Sequence Data Multigene Family/genetics Protein Structure, Tertiary RecQ Helicases
Chemicals
Adenosine Triphosphatases RECQL protein, human RecQ protein, E coli DNA Helicases RecQ Helicases
Authors & Affiliations
3 authors, click to expand affiliations / ORCID
Bernstein Douglas A
Department of Biomolecular Chemistry, 550 Medical Science Center, 1300 University Avenue, University of Wisconsin Medical School, Madison, WI 53706-1532, USA.
Zittel Morgan C
Keck James L
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Article Info
Journal
The EMBO journal
Abbr.
EMBO J
ISSN
0261-4189
DOI
10.1093/emboj/cdg500
Published
2003-10-01
Pages
4910-21
Language
English
Region
England
NLM ID
8208664
PMCID
PMC204483
Subset
IM
Grants
NIGMS NIH HHS · R01 GM068061 · United States
NIGMS NIH HHS · T32 GM008293 · United States
NIGMS NIH HHS · GM068061 · United States
NIGMS NIH HHS · GM08293 · United States
Databases
PDB
1OYW, 1OYY
External Links
PubMed source DOI: 10.1093/emboj/cdg500 PMC Full Text View journal details
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