3HL8

Crystal structure of exonuclease I in complex with inhibitor BCBP


Experimental Data Snapshot

  • Method: X-RAY DIFFRACTION
  • Resolution: 1.55 Å
  • R-Value Free: 0.207 
  • R-Value Work: 0.172 
  • R-Value Observed: 0.174 

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Ligand Structure Quality Assessment 


This is version 1.4 of the entry. See complete history


Literature

Small-molecule tools for dissecting the roles of SSB/protein interactions in genome maintenance

Lu, D.Bernstein, D.A.Satyshur, K.A.Keck, J.L.

(2010) Proc Natl Acad Sci U S A 107: 633-638

  • DOI: https://doi.org/10.1073/pnas.0909191107
  • Primary Citation of Related Structures:  
    3HL8, 3HP9

  • PubMed Abstract: 

    Bacterial single-stranded DNA-binding proteins (SSBs) help to recruit a diverse array of genome maintenance enzymes to their sites of action through direct protein interactions. For all cases examined to date, these interactions are mediated by the evolutionarily conserved C terminus of SSB (SSB-Ct). The essential nature of SSB protein interactions makes inhibitors that block SSB complex formation valuable biochemical tools and attractive potential antibacterial agents. Here, we identify four small molecules that disrupt complexes formed between Escherichia coli SSB and Exonuclease I (ExoI), a well-studied SSB-interacting enzyme. Each compound disrupts ExoI/SSB-Ct peptide complexes and abrogates SSB stimulation of ExoI nuclease activity. Structural and biochemical studies support a model for three of the compounds in which they compete with SSB for binding to ExoI. The fourth appears to rely on an allosteric mechanism to disrupt ExoI/SSB complexes. Subsets of the inhibitors block SSB-Ct complex formation with two other SSB-interaction partners as well, which highlights their utility as reagents for investigating the roles of SSB/protein interactions in diverse DNA replication, recombination, and repair reactions.


  • Organizational Affiliation

    Department of Biomolecular Chemistry, University of Wisconsin School of Medicine and Public Health, Madison, WI 53706, USA.


Macromolecules
Find similar proteins by:  (by identity cutoff)  |  3D Structure
Entity ID: 1
MoleculeChains Sequence LengthOrganismDetailsImage
Exodeoxyribonuclease I482Escherichia coli K-12Mutation(s): 0 
Gene Names: b2011cpeAJW1993sbcBxonA
EC: 3.1.11.1
UniProt
Find proteins for P04995 (Escherichia coli (strain K12))
Explore P04995 
Go to UniProtKB:  P04995
Entity Groups  
Sequence Clusters30% Identity50% Identity70% Identity90% Identity95% Identity100% Identity
UniProt GroupP04995
Sequence Annotations
Expand
  • Reference Sequence
Small Molecules
Ligands 4 Unique
IDChains Name / Formula / InChI Key2D Diagram3D Interactions
BBP
Query on BBP

Download Ideal Coordinates CCD File 
C [auth A](5R)-3-tert-butyl-1-(6-chloro-1,3-benzothiazol-2-yl)-4,5-dihydro-1H-pyrazol-5-ol
C14 H16 Cl N3 O S
SDNWRBUDQKRGSP-GFCCVEGCSA-N
DMS
Query on DMS

Download Ideal Coordinates CCD File 
D [auth A],
E [auth A]
DIMETHYL SULFOXIDE
C2 H6 O S
IAZDPXIOMUYVGZ-UHFFFAOYSA-N
EDO
Query on EDO

Download Ideal Coordinates CCD File 
F [auth A],
G [auth A],
H [auth A]
1,2-ETHANEDIOL
C2 H6 O2
LYCAIKOWRPUZTN-UHFFFAOYSA-N
MG
Query on MG

Download Ideal Coordinates CCD File 
B [auth A]MAGNESIUM ION
Mg
JLVVSXFLKOJNIY-UHFFFAOYSA-N
Binding Affinity Annotations 
IDSourceBinding Affinity
BBP PDBBind:  3HL8 Ki: 3.20e+4 (nM) from 1 assay(s)
Binding MOAD:  3HL8 Ki: 3.20e+4 (nM) from 1 assay(s)
Experimental Data & Validation

Experimental Data

  • Method: X-RAY DIFFRACTION
  • Resolution: 1.55 Å
  • R-Value Free: 0.207 
  • R-Value Work: 0.172 
  • R-Value Observed: 0.174 
  • Space Group: P 21 21 21
Unit Cell:
Length ( Å )Angle ( ˚ )
a = 53.823α = 90
b = 91.966β = 90
c = 106.28γ = 90
Software Package:
Software NamePurpose
PHASERphasing
REFMACrefinement
MAR345data collection
HKL-2000data reduction
SCALEPACKdata scaling

Structure Validation

View Full Validation Report



Ligand Structure Quality Assessment 


Entry History 

Deposition Data

Revision History  (Full details and data files)

  • Version 1.0: 2010-01-19
    Type: Initial release
  • Version 1.1: 2011-07-13
    Changes: Source and taxonomy, Version format compliance
  • Version 1.2: 2014-05-28
    Changes: Other
  • Version 1.3: 2017-11-01
    Changes: Refinement description
  • Version 1.4: 2023-09-06
    Changes: Data collection, Database references, Derived calculations, Refinement description