%0 Journal Article
%T Enzymatic properties of Staphylococcus aureus adenosine synthase (AdsA)
%A Vilasack Thammavongsa
%A Olaf Schneewind
%A Dominique M Missiakas
%J BMC Biochemistry
%D 2011
%I BioMed Central
%R 10.1186/1471-2091-12-56
%X NTPDase ACR motifs are absent in AdsA, yet we report here that recombinant AdsA hydrolyzes ADP and ATP in addition to AMP. Competition assays suggest that hydrolysis occurs following binding of all three substrates at a unique site. Alanine substitution of two amino acids, aspartic acid 127 and histidine 196 within the 5'-nucleotidase signature sequence, leads to reduced AMP or ADP hydrolysis but does not affect the binding of these substrates.Collectively, these results provide insight into the unique ability of AdsA to produce adenosine through the consecutive hydrolysis of ATP, ADP and AMP, thereby endowing S. aureus with the ability to modulate host immune responses.Staphylococcus aureus is a Gram-positive pathogen and the leading cause of bloodstream, lower respiratory tract, skin and soft tissue infections [1]. S. aureus produces numerous virulence factors that contribute to its ability to cause disease [2-4]. These include several toxins that are known for their detrimental effects on host cells [5,6], in particular cells of the immune system [7,8]. Staphylococci can infect a broad range of tissues and organs resulting in excessive tissue damage [9]. This observation is highlighted by the appearance of large populations of necrotic cells surrounding staphylococcal communities within organ abscesses isolated from infected mice [10]. Cellular damage caused by bacterial triggers the release of otherwise sequestered intracellular components such as heat shock proteins (HSPs) [11], S100 proteins [12], nucleosomes [13], N-formylated mitochondrial peptides [14] and purines (ATP and ADP) [15,16] all of which are known to potently stimulate inflammation. Excessive inflammation can be detrimental to the host due to the prolonged presence of activated immune cells as well as the leakage of proteases and other noxious agents that damage surrounding tissues. A delicate balance of pro- and anti-inflammatory mediators is critical to prevent extensive inflammation.Extracellu
%U http://www.biomedcentral.com/1471-2091/12/56