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PMID: 7664751 Published · ppublish English Journal Article Research Support, U.S. Gov't, P.H.S.

Novel DNA binding motifs in the DNA repair enzyme endonuclease III crystal structure.

The EMBO journal ·Vol. 14 ·No. 16 ·1995-08-15 ·Pages 4108-20

Thayer MM, Ahern H, Xing D, Cunningham RP, Tainer JA

Abstract

The 1.85 A crystal structure of endonuclease III, combined with mutational analysis, suggests the structural basis for the DNA binding and catalytic activity of the enzyme. Helix-hairpin-helix (HhH) and [4Fe-4S] cluster loop (FCL) motifs, which we have named for their secondary structure, bracket the cleft separating the two alpha-helical domains of the enzyme. These two novel DNA binding motifs and the solvent-filled pocket in the cleft between them all lie within a positively charged and sequence-conserved surface region. Lys120 and Asp138, both shown by mutagenesis to be catalytically important, lie at the mouth of this pocket, suggesting that this pocket is part of the active site. The positions of the HhH motif and protruding FCL motif, which contains the DNA binding residue Lys191, can accommodate B-form DNA, with a flipped-out base bound within the active site pocket. The identification of HhH and FCL sequence patterns in other DNA binding proteins suggests that these motifs may be a recurrent structural theme for DNA binding proteins.

Related Genes
nth
MeSH Terms
Amino Acid Sequence Binding Sites Conserved Sequence/genetics Crystallography, X-Ray DNA Mutational Analysis DNA Repair DNA-Binding Proteins/chemistry Deoxyribonuclease (Pyrimidine Dimer) Endodeoxyribonucleases/chemistry Genes, Bacterial Helix-Loop-Helix Motifs Iron Lysine Models, Molecular Molecular Sequence Data Mutation Protein Conformation Protein Folding Protein Structure, Secondary Sulfur
Chemicals
DNA-Binding Proteins Sulfur Iron Endodeoxyribonucleases Deoxyribonuclease (Pyrimidine Dimer) Lysine
Authors & Affiliations
5 authors, click to expand affiliations / ORCID
Thayer M M
Scripps Research Institute, Department of Molecular Biology-MB4, La Jolla, CA 92037, USA.
Ahern H
Xing D
Cunningham R P
Tainer J A
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Article Info
Journal
The EMBO journal
Abbr.
EMBO J
ISSN
0261-4189
Published
1995-08-15
Pages
4108-20
Language
English
Region
England
NLM ID
8208664
PMCID
PMC394490
Subset
IM
Grants
NIA NIH HHS · AG00080 · United States
NIGMS NIH HHS · GM46312 · United States
External Links
PubMed source PMC Full Text View journal details
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