Streptococcus pneumoniae Genome‐wide Identification and Characterization of BOX Element‐binding Domains. Issue 11 (6th August 2015)

• Record Type: Journal Article
• Authors: Zhang, Qiao; Wang, Changzheng; Wan, Min; Wu, Yin; Ma, Qianli
• Is Part Of: Molecular informatics. Volume 34:Issue 11/12(2015)
• Page Start: 742
• Page End: 752
• Publication Date: 2015-08-06
• Subjects: BOX element -- DNA‐binding domain -- quantitative structure‐activity relationship -- Streptococcus pneumoniae genome; Cheminformatics -- Periodicals; QSAR (Biochemistry) -- Periodicals; Structure-activity relationships (Biochemistry) -- Periodicals; Drugs -- Structure-activity relationships -- Periodicals; 615.19
• DOI: 10.1002/minf.201500044
• Languages: English
• ISSNs: 1868-1743

Abstract

Abstract: The BOX elements are short repetitive DNA sequences that distribute randomly in intergenic regions of the Streptococcus pneumoniae genome. The function and origin of such elements are still unknown, but they were found to modulate expression of neighboring genes. Evidences suggested that the modulation's mechanism can be fulfilled by sequence‐specific interaction of BOX elements with transcription factor family proteins. However, the type and function of these BOX‐binding proteins still remain largely unexplored to date. In the current study we described a synthetic protocol to investigate the recognition and interaction between a highly conserved site of BOX elements and the DNA‐binding domains of a variety of putative transcription factors in the pneumococcal genome. With the protocol we were able to predict those high‐affinity domain binders of the conserved BOX DNA site (BOX DNA) in a high‐throughput manner, and analyzed sequence‐specific interaction in the domainDNA recognition at molecular level. Consequently, a number of putative transcription factor domains with both high affinity and specificity for the BOX DNA were identified, from which the helix‐turn‐helix (HTH) motif of a small heat shock factor was selected as a case study and tested for its binding capability toward the double‐stranded BOX DNA using fluorescence anisotropy analysis. As might be expected, a relatively high affinity was detected for the interaction of HTH motif with BOX DNA with dissociation constant at nanomolar level. Molecular dynamics simulation, atomic structure examination and binding energy analysis revealed a complicated network of intensive nonbonded interactions across the complex interface, which confers both stability and specificity for the complex architecture. Abstract :