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Biochem Biophys Res Commun. 2018 Oct 12;504(4):704-708. doi: 10.1016/j.bbrc.2018.08.188. Epub 2018 Sep 11.

Crystal structure of SSB complexed with inhibitor myricetin.

Author information

1
School of Biomedical Sciences, Chung Shan Medical University, No.110, Sec.1, Chien-Kuo N. Rd., Taichung City, Taiwan; Department of Medical Research, Chung Shan Medical University Hospital, No.110, Sec.1, Chien-Kuo N. Rd, Taichung City, Taiwan. Electronic address: cyhuang@csmu.edu.tw.

Abstract

Single-stranded DNA-binding protein (SSB) is essential for all DNA-dependent cellular processes. SSB inhibitors have been recently suggested as broad-spectrum antibacterial agents in antibiotic development. In this paper, we report the first inhibitor-complexed crystal structure of SSB from Pseudomonas aeruginosa PAO1 (PaSSB) at 2.68 Å resolution (PDB entry 5YUN). The inhibitor, myricetin, is a flavonol that possesses many pharmacological activities, such as anticancer, anti-inflammatory, and antibacterial properties, and is beneficial for humans. Four monomers of PaSSB and two of myricetins were found per asymmetric unit. Various interactions between myricetin and PaSSB were examined. Among these, four residues in PaSSB, Lys7, Arg62, Glu80, and Gly107 were found crucial for forming hydrogen bond to myricetin. These two myricetins occupy the grooves for ssDNA-binding of SSB that may prevent ssDNA-wrapping and ssDNA-binding stably from SSB. In addition to explaining how SSB can be inhibited, the myricetin-SSB interaction modes in this paper may also provide insights into how myricetin can bind and inhibit proteins on cancer-signaling pathways.

KEYWORDS:

Antibiotics; Myricetin; SSB; SsbA; SsbB; SsbC

PMID:
30213633
DOI:
10.1016/j.bbrc.2018.08.188
[Indexed for MEDLINE]

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