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Bacterial SSB interactome: Structural basis of interaction between E. coli Exonuclease I and SSB and exploitation of this interaction to identify novel anti‐bacterial compounds
Author(s) -
Lu Duo,
Bernstein Douglas,
Keck James
Publication year - 2009
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.23.1_supplement.836.3
Subject(s) - interactome , exonuclease , dna , biology , genome , computational biology , protein–protein interaction , docking (animal) , dna replication , retrotransposon , chemical biology , microbiology and biotechnology , genetics , chemistry , polymerase , gene , transposable element , medicine , nursing
Bacterial single‐strand (ss) DNA‐binding proteins (SSBs) play essential protective and organizational roles in genome biology. To shield ssDNA from potential damage, SSBs bind tightly to ssDNA that arises during the course of DNA replication and repair. Far from being inert, ssDNA/SSB complexes are active DNA processing centers where at least a dozen different enzymes gain access to genomic substrates by exploiting direct protein‐protein interactions with SSB. In all cases examined to date, the last 8‐10 residues of SSB's flexible C‐terminus (SSB‐Ct) form a docking site for heterologous proteins. How proteins bind to the SSB‐Ct sequence and how these essential interactions affect the activities of genome maintenance enzymes remains poorly defined. Moreover, given the essential nature of interactions with SSB, inhibitors that block association with SSB could provide novel avenues for antibiotic development. In our poster, we describe two recent advances from our lab that shed light on these aspects of genome biology. The first defines the physical basis underlying interaction between E. coli Exonuclease I and SSB through a crystallographic approach. The second uses a high‐throughput screen to identify small‐molecule inhibitors that disrupt formation of Exonuclease I/SSB complexes. These inhibitors have robust selective anti‐bacterial properties.