The Overall Architecture and Receptor Binding of Pneumococcal Carbohydrate-Antigen-Hydrolyzing Enzymes

Higgins, M.A.; Ficko-Blean, E.; Meloncelli, Peter J.; Lowary, Todd L.; Boraston, A.B.

doi:10.1016/j.jmb.2011.06.035

Cited by 24 publications

(40 citation statements)

References 50 publications

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“…A common property of the surface-attached pneumococcal enzymes is their multimodularity, but the structures and functions of the modules comprising these important enzymes are not well studied. Of these enzymes, at present, only the surface-attached enzyme SpuA and the secreted family 98 blood group antigen-specific glycoside hydrolases (GH98) have been conclusively demonstrated to have CBMs (49–51). In SpuA, one of the CBM41 modules closes over the active site, aiding directly in substrate recognition, whereas a second module is oriented away from the active site and cell surface to presumably function in adherence to glycogen (52).…”

Section: Discussionmentioning

confidence: 99%

“…In SpuA, one of the CBM41 modules closes over the active site, aiding directly in substrate recognition, whereas a second module is oriented away from the active site and cell surface to presumably function in adherence to glycogen (52). In the GH98 enzymes, the CBMs are oriented away from the active site and probably function to target these soluble enzymes to glycans on host-cell surfaces (51). …”

Section: Discussionmentioning

confidence: 99%

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Conformational Analysis of the Streptococcus pneumoniae Hyaluronate Lyase and Characterization of Its Hyaluronan-specific Carbohydrate-binding Module

Suits

Pluvinage

Law

et al. 2014

Journal of Biological Chemistry

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Background: Hyl from Streptococcus pneumoniae degrades host hyaluronan, an important polysaccharide component of the mammalian extracellular matrix.Results: Hyl has a hyaluronan-specific carbohydrate-binding module, an extended conformation, and a propensity to dimerize.Conclusion: Hyl both binds and degrades hyaluronan, which is facilitated by its cell surface presentation.Significance: This is the first structural and functional characterization of a glycosaminoglycan-specific carbohydrate-binding module.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Conformational Analysis of the Streptococcus pneumoniae Hyaluronate Lyase and Characterization of Its Hyaluronan-specific Carbohydrate-binding Module

Suits

Pluvinage

Law

et al. 2014

Journal of Biological Chemistry

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“…CBMs were labeled by coupling to Alexa Fluor® 488 labeled streptavidin via a biotin-NTA:Ni 2+ linker using methods identical to those described previously [36]. Labeled proteins were desalted using PD-10 columns (GE Healthcare) and used to probe the printed glycan arrays according to the standard procedures of Core H of the Consortium for Functional Glycomics.…”

Section: Methodsmentioning

confidence: 99%

Carbohydrate Recognition by an Architecturally Complex α-N-Acetylglucosaminidase from Clostridium perfringens

et al. 2012

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CpGH89 is a large multimodular enzyme produced by the human and animal pathogen Clostridium perfringens. The catalytic activity of this exo-α-d-N-acetylglucosaminidase is directed towards a rare carbohydrate motif, N-acetyl-β-d-glucosamine-α-1,4-d-galactose, which is displayed on the class III mucins deep within the gastric mucosa. In addition to the family 89 glycoside hydrolase catalytic module this enzyme has six modules that share sequence similarity to the family 32 carbohydrate-binding modules (CBM32s), suggesting the enzyme has considerable capacity to adhere to carbohydrates. Here we suggest that two of the modules, CBM32-1 and CBM32-6, are not functional as carbohydrate-binding modules (CBMs) and demonstrate that three of the CBMs, CBM32-3, CBM32-4, and CBM32-5, are indeed capable of binding carbohydrates. CBM32-3 and CBM32-4 have a novel binding specificity for N-acetyl-β-d-glucosamine-α-1,4-d-galactose, which thus complements the specificity of the catalytic module. The X-ray crystal structure of CBM32-4 in complex with this disaccharide reveals a mode of recognition that is based primarily on accommodation of the unique bent shape of this sugar. In contrast, as revealed by a series of X-ray crystal structures and quantitative binding studies, CBM32-5 displays the structural and functional features of galactose binding that is commonly associated with CBM family 32. The functional CBM32s that CpGH89 contains suggest the possibility for multivalent binding events and the partitioning of this enzyme to highly specific regions within the gastrointestinal tract.

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“…Terra et al Fig. [143]); FcsSBP (2W7Y); FcsI (4C22); FcsK (4C23); FcsA (4C25). Schematic depiction of the release and processing of fucose from fucosylated glycans.…”

Section: O-glycan Degradation Multipathway Proteins and Pneumococcalmentioning

confidence: 97%

“…BgaC has been shown to contribute to the growth of S. pneumoniae on mucin, suggesting a possible role in nutrient acquisition [129]; however, findings regarding its effect on virulence in mouse models are conflicting. [143]); EIIA fuc (5T3U); EIIB fuc (5T5D); FcsU (4A34); Sp3GH98 (SAXS model Ref. 2.…”

Section: O-glycan Degradation Multipathway Proteins and Pneumococcalmentioning

confidence: 99%

Glycan‐metabolizing enzymes in microbe–host interactions: the Streptococcus pneumoniae paradigm

2018

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Streptococcus pneumoniae is a frequent colonizer of the upper airways; however, it is also an accomplished pathogen capable of causing life-threatening diseases. To colonize and cause invasive disease, this bacterium relies on a complex array of factors to mediate the host-bacterium interaction. The respiratory tract is rich in functionally important glycoconjugates that display a vast range of glycans, and, thus, a key component of the pneumococcus-host interaction involves an arsenal of bacterial carbohydrate-active enzymes to depolymerize these glycans and carbohydrate transporters to import the products. Through the destruction of host glycans, the glycan-specific metabolic machinery deployed by S. pneumoniae plays a variety of roles in the host-pathogen interaction. Here, we review the processing and metabolism of the major host-derived glycans, including N- and O-linked glycans, Lewis and blood group antigens, proteoglycans, and glycogen, as well as some dietary glycans. We discuss the role of these metabolic pathways in the S. pneumoniae-host interaction, speculate on the potential of key enzymes within these pathways as therapeutic targets, and relate S. pneumoniae as a model system to glycan processing in other microbial pathogens.

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The Overall Architecture and Receptor Binding of Pneumococcal Carbohydrate-Antigen-Hydrolyzing Enzymes

Cited by 24 publications

References 50 publications

Conformational Analysis of the Streptococcus pneumoniae Hyaluronate Lyase and Characterization of Its Hyaluronan-specific Carbohydrate-binding Module

Conformational Analysis of the Streptococcus pneumoniae Hyaluronate Lyase and Characterization of Its Hyaluronan-specific Carbohydrate-binding Module

Carbohydrate Recognition by an Architecturally Complex α-N-Acetylglucosaminidase from Clostridium perfringens

Glycan‐metabolizing enzymes in microbe–host interactions: the Streptococcus pneumoniae paradigm

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