Search

The review is focused on the bacterial protein tyrosine phosphatases (PTPs) utilized by bacteria as virulence factors necessary for pathogenicity. The inhibition of bacterial PTPs could contribute to the arrest of the bacterial infection process. This mechanism could be utilized in the design of antimicrobial therapy as adjuvants to antibiotics. The review summaries knowledge on pathogenic bacterial protein tyrosine phosphatases (PTPs) involved in infection process, such as: PTPA and PTPB from Staphylococcus aureus and Mycobacterium tuberculosis; SptP from Salmonella typhimurium; YopH from Yersinia sp. and TbpA from Pseudomonas aeruginosa. The review focuses also on the potential inhibitory compounds of bacterial virulence factors and inhibitory mechanisms such as the reversible oxidation of tyrosine phosphatases. [ABSTRACT FROM AUTHOR]

The review is focused on the bacterial protein tyrosine phosphatases (PTPs) utilized by bacteria as virulence factors necessary for pathogenicity. The inhibition of bacterial PTPs could contribute to the arrest of the bacterial infection process. This mechanism could be utilized in the design of antimicrobial therapy as adjuvants to antibiotics. The review summaries knowledge on pathogenic bacterial protein tyrosine phosphatases (PTPs) involved in infection process, such as: PTPA and PTPB from Staphylococcus aureus and Mycobacterium tuberculosis; SptP from Salmonella typhimurium; YopH from Yersinia sp. and TbpA from Pseudomonas aeruginosa. The review focuses also on the potential inhibitory compounds of bacterial virulence factors and inhibitory mechanisms such as the reversible oxidation of tyrosine phosphatases.

Abstract: AphA is a magnesium-dependent, bacterial class B acid phosphatase that catalyzes the hydrolysis of a variety of phosphoester substrates and belongs to the DDDD superfamily of phosphohydrolases. The recently reported crystal structure of AphA from Escherichia coli has revealed the quaternary structure of the enzyme together with hints about its catalytic mechanism. The present work reports the crystal structures of AphA from E. coli in complex with substrate, transition-state, and intermediate analogues. The structures provide new insights into the mechanism of the enzyme and allow a revision of some aspects of the previously proposed mechanism that have broader implications for all the phosphatases of the DDDD superfamily. [Copyright &y& Elsevier]

The Escherichia coli gene aphA codes for a periplasmic acid phosphatase called AphA, belonging to class B bacterial phosphatases, which is part of the DDDD superfamily of phosphohydrolases. After our first report about its crystal structure, we have started a series of crystallographic studies aimed at understanding of the catalytic mechanism of the enzyme. Here, we report three crystal structures of the AphA enzyme in complex with the hydrolysis products of nucleoside monophosphate substrates and a fourth with a proposed intermediate analogue that appears to be covalently bound to the enzyme. Comparison with the native enzyme structure and with the available X-ray structures of different phosphatases provides clues about the enzyme chemistry and allows us to propose a catalytic mechanism for AphA, and to discuss it with respect to the mechanism of other bacterial and human phosphatases. [Copyright &y& Elsevier]