3QSB

Structure of E. coli polIIIbeta with (Z)-5-(1-((4'-Fluorobiphenyl-4-yl)methoxyimino)butyl)-2,2-dimethyl-4,6-dioxocyclohexanecarbonitrile

Summary for 3QSB

• Entry DOI: 10.2210/pdb3qsb/pdb
• Related: 1MMI 2POL
• Descriptor: DNA polymerase III subunit beta, (1R,5R)-5-{(1Z)-N-[(4'-fluorobiphenyl-4-yl)methoxy]butanimidoyl}-2,2-dimethyl-4,6-dioxocyclohexanecarbonitrile, ... (4 entities in total)
• Functional Keywords: dna replication, sliding clamp, dnan, transferase-transferase inhibitor complex, transferase/transferase inhibitor
• Biological source: Escherichia coli; More
• Cellular location: Cytoplasm : P0A988 P0A988
• Total number of polymer chains: 2
• Total formula weight: 82146.02

Authors

Wijffels, G.,Johnson, W.M.,Oakley, A.J.,Turner, K.,Epa, V.C.,Briscoe, S.J.,Polley, M.,Liepa, A.J.,Hofmann, A.,Buchardt, J.,Christensen, C.,Prosselkov, P.,Dalrymple, B.P.,Alewood, P.F.,Jennings, P.A.,Dixon, N.E.,Winkler, D.A. (deposition date: 2011-02-20, release date: 2011-06-08, Last modification date: 2024-10-30)

Primary citation

Wijffels, G.,Johnson, W.M.,Oakley, A.J.,Turner, K.,Epa, V.C.,Briscoe, S.J.,Polley, M.,Liepa, A.J.,Hofmann, A.,Buchardt, J.,Christensen, C.,Prosselkov, P.,Dalrymple, B.P.,Alewood, P.F.,Jennings, P.A.,Dixon, N.E.,Winkler, D.A.
Binding inhibitors of the bacterial sliding clamp by design
J.Med.Chem., 54:4831-4838, 2011

PubMed Abstract: The bacterial replisome is a target for the development of new antibiotics to combat drug resistant strains. The β(2) sliding clamp is an essential component of the replicative machinery, providing a platform for recruitment and function of other replisomal components and ensuring polymerase processivity during DNA replication and repair. A single binding region of the clamp is utilized by its binding partners, which all contain conserved binding motifs. The C-terminal Leu and Phe residues of these motifs are integral to the binding interaction. We acquired three-dimensional structural information on the binding site in β(2) by a study of the binding of modified peptides. Development of a three-dimensional pharmacophore based on the C-terminal dipeptide of the motif enabled identification of compounds that on further development inhibited α-β(2) interaction at low micromolar concentrations. We report the crystal structure of the complex containing one of these inhibitors, a biphenyl oxime, bound to β(2), as a starting point for further inhibitor design.

PubMed: 21604761
DOI: 10.1021/jm2004333

Experimental method

X-RAY DIFFRACTION (1.9 Å)