Peptides as Inhibitors of the First Phosphorylation Step of the Streptomyces coelicolor Phosphoenolpyruvate: Sugar Phosphotransferase System
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- 作者：Rosa Dom茅nech ; Sergio Mart铆nez-Rodr铆guez ; Adri谩n Vel谩zquez-Campoy ; Jos茅 L. Neira
- 刊名：Biochemistry
- 出版年：2012
- 出版时间：September 18, 2012
- 年：2012
- 卷：51
- 期：37
- 页码：7393-7402
- 全文大小：368K
- 年卷期：v.51,no.37(September 18, 2012)
- ISSN：1520-4995
文摘
The phosphotransferase system (PTS) controls the use of sugars in bacteria. The PTS is ubiquitous in bacteria, but it does not occur in plants and animals; it modulates catabolite repression, intermediate metabolism, gene expression, and chemotaxis. Its uniqueness and pleiotropic function make the PTS an attractive target for new antibacterial drugs. The PTS is constituted of two general proteins, namely, enzyme I (EI) and the histidine phosphocarrier (HPr), and various sugar-specific permeases. EI has two domains: the N-terminal domain (EIN), which binds to HPr, and the C-terminal domain (EIC), which contains the dimerization interface. In this work, we determined the binding affinities of peptides derived from EIN of Streptomyces coelicolor (EINsc) against HPr of the same organism (HPrsc), by using nuclear magnetic resonance and isothermal titration calorimetry techniques. Furthermore, we measured the affinity of EINsc for (i) a peptide derived from HPrsc, containing the active-site histidine, and (ii) other peptides identified previously by phage display and combinatorial chemistry in Escherichia coli [Mukhija, S. L., et al (1998) Eur. J. Biochem. 254, 433鈥?38; Mukhija, S., and Erni, B. (1997) Mol. Microbiol. 25, 1159鈥?166]. The affinities were in the range of 10 渭M, being slightly higher for the binding of EINsc with peptides derived from HPrsc, phage display, or combinatorial chemistry (KD 5 渭M). Because the affinity of intact EINsc for the whole HPrsc is 12 渭M, we suggest that the assayed peptides might be considered as good hit compounds for inhibiting the interaction between HPrsc and EINsc.