4U8C

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

4U8C の概要

• エントリーDOI: 10.2210/pdb4u8c/pdb
• 関連するPDBエントリー: 4U8A 4U8B
• 分子名称: 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)
• 機能のキーワード: antibacterial agents, bisamidines, minor groove binders, models, molecular, nucleic acid conformation, oligodeoxyribonucleotides, dna-antibiotic complex, dna/antibiotic
• 由来する生物種: synthetic construct
• タンパク質・核酸の鎖数: 2
• 化学式量合計: 7823.67

構造登録者

Zhu, W.,Oldfield, E. (登録日: 2014-08-01, 公開日: 2015-02-04, 最終更新日: 2023-09-27)

主引用文献

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

実験手法

X-RAY DIFFRACTION (1.24 Å)