Abstract:
:Bacterial sliding clamps control the access of DNA polymerases to the replication fork and are appealing targets for antibacterial drug development. It is therefore essential to decipher the polymerase-clamp binding mode across various bacterial species. Here, two residues of the E. coli clamp binding pocket, EcS346 and EcM362, and their cognate residues in M. tuberculosis and B. subtilis clamps, were mutated. The effects of these mutations on the interaction of a model peptide with these variant clamps were evaluated by thermodynamic, molecular dynamics, X-rays crystallography, and biochemical analyses. EcM362 and corresponding residues in Gram positive clamps occupy a strategic position where a mobile residue is essential for an efficient peptide interaction. EcS346 has a more subtle function that modulates the pocket folding dynamics, while the equivalent residue in B. subtilis is essential for polymerase activity and might therefore be a Gram positive-specific molecular marker. Finally, the peptide binds through an induced-fit process to Gram negative and positive pockets, but the complex stability varies according to a pocket-specific network of interactions.
journal_name
ACS Infect Disjournal_title
ACS infectious diseasesauthors
André C,Martiel I,Wolff P,Landolfo M,Lorber B,Silva da Veiga C,Dejaegere A,Dumas P,Guichard G,Oliéric V,Wagner J,Burnouf DYdoi
10.1021/acsinfecdis.9b00089subject
Has Abstractpub_date
2019-06-14 00:00:00pages
1022-1034issue
6issn
2373-8227journal_volume
5pub_type
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