title: RshA mimetic peptides inhibiting the transcription driven by a Mycobacterium tuberculosis sigma factor SigH.
abstract: SigH, an alternative sigma factor in Mycobacterium tuberculosis, is a central regulator in responses to the oxidative and heat stress. This SigH activity is specifically controlled by an anti-sigma factor RshA during expression of stress-related genes. Thus, the specific interaction (k(on)=1.15x10(5) (M(-1) s(-1)), k(off)=1.7x10(-3) (s(-1)), KD=15 nM, determined in this study) between SigH and RshA is crucial for the survival and pathogenesis of M. tuberculosis. Using phage-display peptide library, we defined three specific regions on RshA responsible for SigH binding. Three RshA mimetic peptides (DAHADHD, AEVWTLL, and CTPETRE) specifically inhibited the transcription initiated by SigH in vitro. One of them (DAHADHD) diminished the extent of binding of RshA to SigH in a dose-dependent manner. The binding affinity (KD) of this peptide to SigH was about 1.2 microM. These findings might provide some insights into the development of new peptide-based drugs for TB.
authors.affiliation: Department of Biochemistry and RINS, College of Medicine and Gyeongsang Institute of Health Sciences, Gyeongsang National University, JinJu, Republic of Korea.
authors.forename: Eun Hee
authors.initials: EH
authors.lastname: Jeong
authors.forename: Young Mi
authors.initials: YM
authors.lastname: Son
authors.forename: Young-Sool
authors.initials: YS
authors.lastname: Hah
authors.forename: Yeon Jin
authors.initials: YJ
authors.lastname: Choi
authors.forename: Kon Ho
authors.initials: KH
authors.lastname: Lee
authors.forename: Taeksun
authors.initials: T
authors.lastname: Song
authors.forename: Deok Ryong
authors.initials: DR
authors.lastname: Kim
mesh_terms: D000595:Amino Acid Sequence; D001426:Bacterial Proteins / Q000235:genetics / Q000378:metabolism*; D047908:Intracellular Signaling Peptides and Proteins / Q000737:chemistry / Q000378:metabolism*; D008969:Molecular Sequence Data; D009169:Mycobacterium tuberculosis / Q000378:metabolism*; D019151:Peptide Library; D010455:Peptides / Q000494:pharmacology*; D011485:Protein Binding; D012808:Sigma Factor / Q000235:genetics / Q000378:metabolism*; D020349:Surface Plasmon Resonance; D014158:Transcription, Genetic
chemical_list: D001426:Bacterial Proteins; D047908:Intracellular Signaling Peptides and Proteins; D019151:Peptide Library; D010455:Peptides; C480851:RshA protein, Mycobacterium tuberculosis; C120328:SigH protein, bacteria; D012808:Sigma Factor