3HP9

Crystal structure of SSB/Exonuclease I in complex with inhibitor CFAM

Summary for 3HP9

• Entry DOI: 10.2210/pdb3hp9/pdb
• Related: 3C94 3C95 3HL8
• Descriptor: Exodeoxyribonuclease I, MAGNESIUM ION, 2-{[2-chloro-5-(trifluoromethyl)phenyl]amino}-5-methoxybenzoic acid, ... (6 entities in total)
• Functional Keywords: exonuclease, ssb, genome maintenance, dna damage, dna repair, hydrolase, nuclease
• Biological source: Escherichia coli
• Total number of polymer chains: 1
• Total formula weight: 56333.31

Authors

Satyshur, K.A. (deposition date: 2009-06-03, release date: 2010-01-19, Last modification date: 2023-09-06)

Primary citation

Lu, D.,Bernstein, D.A.,Satyshur, K.A.,Keck, J.L.
Small-molecule tools for dissecting the roles of SSB/protein interactions in genome maintenance
Proc.Natl.Acad.Sci.USA, 107:633-638, 2010

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.

PubMed: 20018747
DOI: 10.1073/pnas.0909191107

Experimental method

X-RAY DIFFRACTION (1.6 Å)