4U8C

Crystal structure of D(CGCGAATTCGCG)2 complexed with BPH-1409

Summary for 4U8C

• Entry DOI: 10.2210/pdb4u8c/pdb
• Related: 4U8A 4U8B
• Descriptor: DNA (5'-D(*CP*GP*CP*GP*AP*AP*TP*TP*CP*GP*CP*G)-3'), MAGNESIUM ION, 2,2'-benzene-1,4-diylbis[6-(1,4,5,6-tetrahydropyrimidin-2-yl)-1H-indole], ... (4 entities in total)
• Functional Keywords: antibacterial agents, bisamidines, minor groove binders, models, molecular, nucleic acid conformation, oligodeoxyribonucleotides, dna-antibiotic complex, dna/antibiotic
• Biological source: synthetic construct
• Total number of polymer chains: 2
• Total formula weight: 7823.67

Authors

Zhu, W.,Oldfield, E. (deposition date: 2014-08-01, release date: 2015-02-04, Last modification date: 2023-09-27)

Primary citation

Zhu, W.,Wang, Y.,Li, K.,Gao, J.,Huang, C.H.,Chen, C.C.,Ko, T.P.,Zhang, Y.,Guo, R.T.,Oldfield, E.
Antibacterial drug leads: DNA and enzyme multitargeting.
J.Med.Chem., 58:1215-1227, 2015

PubMed Abstract: We report the results of an investigation of the activity of a series of amidine and bisamidine compounds against Staphylococcus aureus and Escherichia coli. The most active compounds bound to an AT-rich DNA dodecamer (CGCGAATTCGCG)2 and using DSC were found to increase the melting transition by up to 24 °C. Several compounds also inhibited undecaprenyl diphosphate synthase (UPPS) with IC50 values of 100-500 nM, and we found good correlations (R(2) = 0.89, S. aureus; R(2) = 0.79, E. coli) between experimental and predicted cell growth inhibition by using DNA ΔTm and UPPS IC50 experimental results together with one computed descriptor. We also solved the structures of three bisamidines binding to DNA as well as three UPPS structures. Overall, the results are of general interest in the context of the development of resistance-resistant antibiotics that involve multitargeting.

PubMed: 25574764
DOI: 10.1021/jm501449u

Experimental method

X-RAY DIFFRACTION (1.24 Å)