![]() 21 NanS (YjhS) was annotated as a putative acetylxylan esterase or 9- O-sialic acid esterase and has recently been shown to be capable of using 9- O-acetyl N-acetyl neuraminic acid (Neu5,9Ac 2) as a substrate and is necessary for the ability of E. 20 NanM (YjhT) is a mutarotase which produces the thermodynamically more stable beta form of sialic acid from its corresponding alpha isomer. NanC (YjhA) is an outer membrane porin inducible by Neu5Ac. ![]() The functions of all three enzymes within the nanCMS operon have been assigned. coli, there are three operons, nanATEK- yhcH, nanCMS (formerly yjhATS), and yjhBC, whose enzyme products have been shown or are predicted to be involved in a sialic acid catabolism, and whose expression is regulated by the NanR repressor in response to Neu5Ac concentration-dependent manner. 16, 18 The enzymes in these pathways are coregulated in response to the sialic acid environment that surrounds the pathogen, in particular the presence of the most common form of sialic acid, N-acetyl neuraminic acid (Neu5Ac). The abundance of sialic acid within the host, especially in the mucosal environment, provides a source of carbon and nitrogen for bacteria such as Escherichia coli, which possess pathways to catabolize sialic acid. 16, 17 Some bacteria, in particular pathogenic strains, utilize sialic acid as a decoy molecule, where it is often found as part of the capsular polysaccharide or of lipopolysaccharide, 9 allowing the pathogen to evade the host immune response by masquerading as “self” (reviewed in Ref. In higher organisms, sialic acid (2-keto-3-deoxy-5-acetamido- D- glycero- D- galacto-nonulosonic acid) is usually found as a glycoconjugate, which plays diverse roles in a range of biologically important processes from cell-cell recognition and signaling to neural development. 9- 11 Many of these N- and O-deacetylases show a relatively broad substrate specificity profile with a variety of naturally occurring and synthetic substrates, 12- 14 although some are remarkably specific for their natural substrate, such as the enzymes in carbohydrate esterase family (CE) 2 which are specific for the 6- O-deacetylation of aldohexoses. The deacetylase enzymes can be grouped within two broad functional classes: those that remove acetyl groups from carbohydrate units of polysaccharides, including pectin, 2 xylan, 3 galactoglucomannan, 4 chitin, 5 rhamnogalacturonan, 6 or conjugated sialic acids 7, 8 as part of their catabolism of carbon sources, and those associated with a regulatory or virulence-related function, often found within pathogenic bacteria. Despite its wide occurrence, in many instances, we have an incomplete understanding of the function of carbohydrate acetylation and deacetylation, as well as the enzymes involved in these processes. The multiplicity of enzymes involved in deacetylation is reflected by the classification of carbohydrate esterases within 16 groups in the carbohydrate active enzymes database, CAZy ( 1). ![]() In addition to structural characterization, we have mapped the specificity of NanS using a battery of substrates.Īcetylation of carbohydrates yielding singly or multiple O- or N-acetylated forms and their subsequent deacetylation occurs commonly in nature. The contribution of Ser19 and His301 to catalysis was confirmed by mutagenesis. Its catalytic center contains Ser19 and His301 but no Asp/Glu is present to form the classical catalytic triad. ![]() Although the backbone of the structure is similar to previously characterized family members, sequence comparisons indicate that this family can be further subdivided into two subfamilies with somewhat different fingerprints. Through structural studies, we show that NanS adopts a SGNH hydrolase fold. One such enzyme is NanS, a carbohydrate esterase that we show here deacetylates the 9 position of 9- O-sialic acid so that it can be readily transported into the cell for catabolism. There is a high prevalence of sialic acid in a number of different organisms, resulting in there being a myriad of different enzymes that can exploit it as a fermentable carbon source. ![]()
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