Identifying DNA-binding proteins using structural motifs and the electrostatic potential.

Robust methods to detect DNA-binding proteins from structures of unknown function are important for structural biology. This paper describes a method for identifying such proteins that (i) have a solvent accessible structural motif necessary for DNA-binding and (ii) a positive electrostatic potential in the region of the binding region. We focus on three structural motifs: helix-turn-helix (HTH), helix-hairpin-helix (HhH) and helix-loop-helix (HLH). We find that the combination of these variables detect 78% of proteins with an HTH motif, which is a substantial improvement over previous work based purely on structural templates and is comparable to more complex methods of identifying DNA-binding proteins. Similar true positive fractions are achieved for the HhH and HLH motifs. We see evidence of wide evolutionary diversity for DNA-binding proteins with an HTH motif, and much smaller diversity for those with an HhH or HLH motif.

• Publication year

  2004

• Venue

  Nucleic Acids Research

• Publication date

  Unknown publication date

• Fields of study

  Biology, Medicine, Chemistry

• Identifiers
  DOI 10.1093/NAR/GKH803PMID 15356290PMCID PMC519102
• External record

  Open on Semantic Scholar

• Source metadata

  Semantic Scholar, PubMed

• No claims are published for this paper.

• No concepts are published for this paper.

• The Pfam protein families database

  2007influential reference
• Structural basis for DNA bridging by barrier-to-autointegration factor

  2005cited by this paper
• Using structural motif templates to identify proteins with DNA binding function.

  2003influential reference
• Product-assisted catalysis in base-excision DNA repair

  2003cited by this paper
• Using electrostatic potentials to predict DNA-binding sites on DNA-binding proteins.

  2003cited by this paper
• Full‐length archaeal Rad51 structure and mutants: mechanisms for RAD51 assembly and control by BRCA2

  2003cited by this paper
• Annotating nucleic acid-binding function based on protein structure.

  2003influential reference
• The Pfam protein families database.

  2002cited by this paper
• The PyMOL Molecular Graphics System

  2002cited by this paper
• Recent improvements to the SMART domain-based sequence annotation resource

  2002influential reference
• Common fold in helix-hairpin-helix proteins.

  2000cited by this paper
• Structural basis for recognition and repair of the endogenous mutagen 8-oxoguanine in DNA

  2000cited by this paper
• Helix-Loop-Helix Proteins: Regulators of Transcription in Eucaryotic Organisms

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  2000cited by this paper
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  2000cited by this paper
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  1999cited by this paper
• Implication of tubby proteins as transcription factors by structure-based functional analysis.

  1999cited by this paper
• Conserved domains in DNA repair proteins and evolution of repair systems.

  1999cited by this paper
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  1999cited by this paper
• Structural similarities between Escherichia coli RuvA protein and other DNA-binding proteins and a mutational analysis of its binding to the holliday junction.

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  1998cited by this paper
• Cloning, overproduction, purification and crystallization of the DNA binding protein HU from the hyperthermophilic eubacterium Thermotoga maritima.

  1998cited by this paper
• Co-crystal structure of sterol regulatory element binding protein 1a at 2.3 A resolution.

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• Crystal structures of human DNA polymerase beta complexed with gapped and nicked DNA: evidence for an induced fit mechanism.

  1997cited by this paper
• Crystal structure of PHO4 bHLH domain–DNA complex: flanking base recognition

  1997cited by this paper
• CATH--a hierarchic classification of protein domain structures.

  1997cited by this paper
• The crystal structure of an intact human Max-DNA complex: new insights into mechanisms of transcriptional control.

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• A natural classification of the basic helix-loop-helix class of transcription factors.

  1997cited by this paper
• The helix-hairpin-helix DNA-binding motif: a structural basis for non- sequence-specific recognition of DNA

  1996cited by this paper
• Crystal structures of human DNA polymerase beta complexed with DNA: implications for catalytic mechanism, processivity, and fidelity.

  1996cited by this paper
• Hidden Markov models for sequence analysis: extension and analysis of the basic method

  1996cited by this paper
• SCOP: a structural classification of proteins database for the investigation of sequences and structures.

  1995influential reference
• 脊髄神経細胞の発達におけるHelix-loop-helix transcription factorsの役割について

  1995cited by this paper
• Crystal structure of Thermus aquaticus DNA polymerase

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• RASMOL: biomolecular graphics for all.

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• Crystal structure of MyoD bHLH domain-DNA complex: perspectives on DNA recognition and implications for transcriptional activation.

  1994cited by this paper
• Transcription factors 2: helix-loop-helix.

  1994cited by this paper
• Structure and function of the b/HLH/Z domain of USF.

  1994cited by this paper
• Structure and function of helix-loop-helix proteins.

  1994cited by this paper
• Recognition by Max of its cognate DNA through a dimeric b/HLH/Z domain

  1993cited by this paper
• Refined 1.8 A crystal structure of the lambda repressor-operator complex.

  1992cited by this paper
• Refined 1.8 p crystal structure of the ? repressor-operator complex*1

  1992cited by this paper
• A structural taxonomy of DNA-binding domains

  1991cited by this paper
• Folding transition in the DMA-binding domain of GCN4 on specific binding to DNA

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• A new DNA binding and dimerization motif in immunoglobulin enhancer binding, daughterless, MyoD, and myc proteins.

  1989cited by this paper
• Comparison of the predicted and observed secondary structure of T4 phage lysozyme.

  1975cited by this paper
• Electronic Reprint Biological Crystallography the Protein Data Bank Biological Crystallography the Protein Data Bank

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