Speaker
Mr
Hussain Bhukya
(1. IITB-Monash Research Academy, IIT Bombay, Powai, Mumbai 400076, India. 2. Department of Chemistry, Indian Institute of Technology Bombay, Mumbai 400076, India. 3. Australian Centre for Research on Separation Science (ACROSS), School of Chemistry, Monash University, Melbourne, Victoria 3800, Australia)
Description
Metabolic pathways activated by small chemical signaling molecules in the soil-dwelling, filamentous Gram-positive bacterial genus *Streptomyces* regulate antibiotics production, morphogenesis and resistance mechanisms. These species produce a wide spectrum of biologically active secondary metabolites contributing to > 70% of the known naturally occurring antibiotics. Small diffusible molecules, γ-butyrolactones (GBLs) are signaling molecules in *Streptomyces* and interact with transcriptional regulatory proteins that trigger downstream responses. Their identity and mode of action in *Streptomyces coelicolor* is hitherto unknown. In this investigation, purified CprB, a GBL receptor, was used as an affinity matrix to enrich and identify the target molecule(s) from an extracellular extract of *S. coelicolor*. Results from LC-ESI-MS/MS studies of compounds bound to CprB suggest that there is more than one signaling molecule that controls its DNA binding activity. Furthermore, in order to decipher the structural basis and associated conformational changes during CprB-DNA interaction, we here present a CprB-DNA complex crystal structure at 3.25 Å resolution. CprB binds to the DNA as dimer of dimers via the helix-turn-helix (HTH) motif with the mode of DNA binding analogous to the broad spectrum multidrug resistance regulator QacR from *Staphylococcus aureus*. Binding of the DNA induces restructuring of the CprB dimeric interface, thereby triggering a pendulum-like motion of the HTH motif. Our studies suggest that CprB serves as an autoregulator and is a part of a regulatory network for antibiotic production and resistance pathways responding to signalling molecules in *S. coelicolor*.
| Keywords | Antibiotic production, Resistance, Streptomyces coelicolor, CprB-DNA complex, Signaling molecules, |
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Primary author
Mr
Hussain Bhukya
(1. IITB-Monash Research Academy, IIT Bombay, Powai, Mumbai 400076, India. 2. Department of Chemistry, Indian Institute of Technology Bombay, Mumbai 400076, India. 3. Australian Centre for Research on Separation Science (ACROSS), School of Chemistry, Monash University, Melbourne, Victoria 3800, Australia)
Co-authors
Dr
Chunfang Zhang
(Australian Centre for Research on Separation Science (ACROSS), School of Chemistry, Monash University, Melbourne, Victoria 3800, Australia)
Dr
Khosse Mitri
(Australian Centre for Research on Separation Science (ACROSS), School of Chemistry, Monash University, Melbourne, Victoria 3800, Australia)
Prof.
Milton Hearn
(Australian Centre for Research on Separation Science (ACROSS), School of Chemistry, Monash University, Melbourne, Victoria 3800, Australia)
Dr
Reinhard Boysen
(Australian Centre for Research on Separation Science (ACROSS), School of Chemistry, Monash University, Melbourne, Victoria 3800, Australia)
Prof.
Ruchi Anand
(Department of Chemistry, Indian Institute of Technology Bombay, Mumbai 400076, India)
Dr
Yuanzhong Yang
(Australian Centre for Research on Separation Science (ACROSS), School of Chemistry, Monash University, Melbourne, Victoria 3800, Australia)
