Catalytic preference of Salmonella typhimurium LT2 sialidase for N‐acetylneuraminic acid residues over N‐glycolylneuraminic acid residues

Minami, Akira; Ishibashi, Sayaka; Ikeda, Kiyoshi; Ishitsubo, Erika; Hori, Takuma; Tokiwa, Hiroaki; Taguchi, Risa; Ieno, Daisuke; Otsubo, Tadamune; Matsuda, Yukino; Sai, Saki; Inada, Mari; Suzuki, Takashi

doi:10.1016/j.fob.2013.05.002

Cited by 26 publications

(14 citation statements)

References 38 publications

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“…In general, sialidases are shown to cleave Neu5Ac from glyconconjugates more efficiently than Neu5Gc (Corfield et al, 1981), and species-specific interaction of pathogens and host-structures has been described before, e.g. sialidases of Salmonella spp., and also the pneumococcal sialidase NanC bind stronger to Neu5Ac than to Neu5Gc (Minami et al, 2013; Parker et al, 2012). S. pneumoniae de-glycosylates structures on the surface of host cells with the help of the sialidase NanA (King et al, 2004), and can use Sias as carbon source (Burnaugh et al, 2008; Marion et al, 2011).…”

Section: Discussionmentioning

confidence: 99%

Streptococcus pneumoniae Senses a Human-like Sialic Acid Profile via the Response Regulator CiaR

Hentrich

Löfling

Pathak

et al. 2016

Cell Host & Microbe

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Summary Streptococcus pneumoniae is a human-adapted pathogen that encounters terminally sialylated glycoconjugates and free sialic acid (Sia) in the airways. Upon scavenging by the bacterial sialidase NanA, Sia products serve as carbon sources for the bacteria. Unlike most animals in which cytidine-monophosphate-N-acetylneuraminic acid hydroxylase (CMAH) converts Sia N-acetylneuraminic acid (Neu5Ac) into N-glycolylneuraminic acid (Neu5Gc), humans have an inactive CMAH, causing an absence of Neu5Gc and excess Neu5Ac. We find that pneumococcal challenge in Cmah−/− mice leads to heightened bacterial loads, virulence, and NanA expression. In vitro, NanA is upregulated in response to Neu5Ac compared to Neu5Gc, a process controlled by two-component response regulator CiaR and requiring Sia uptake by the transporter SatABC. Additionally, compared to Neu5Gc, Neu5Ac increases pneumococcal resistance to antimicrobial reactive oxygen species in a CiaR-dependant manner. Thus, S. pneumoniae senses and responds to Neu5Ac, leading to CiaR activation and increased virulence and potentially explaining greater susceptibility in humans.

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Section: Discussionmentioning

confidence: 99%

Streptococcus pneumoniae Senses a Human-like Sialic Acid Profile via the Response Regulator CiaR

Hentrich

Löfling

Pathak

et al. 2016

Cell Host & Microbe

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“…Among gut pathogens, NanH/STSA from S. typhimurium TA262/LT2 strain has been biochemically [ 62 , 63 ] ( Table 1 ) and structurally [ 64 , 65 ] characterized ( Figure 3 A), revealing conservation of key catalytic residues with the GH34 viral sialidases, including the nucleophilic charge relay, the aspartic acid acid/base and the arginine triad. This enzyme shows kinetic preference for sialyl α2-3 linkages over sialyl α2-6 linkages [ 62 ] and preferentially cleaves Neu5Ac residues rather than N -glycolylneuraminic acid (Neu5Gc) residues [ 66 ] ( Table 1 ). Some strains of C. perfringens encode multiple sialidases ( Table 1 ) [ 67 – 74 ].…”

Section: Hydrolytic Exo-sialidasesmentioning

confidence: 99%

Sialidases from gut bacteria: a mini-review

Juge

Tailford

Owen

2016

Biochemical Society Transactions

135

130

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Sialidases are a large group of enzymes, the majority of which catalyses the cleavage of terminal sialic acids from complex carbohydrates on glycoproteins or glycolipids. In the gastrointestinal (GI) tract, sialic acid residues are mostly found in terminal location of mucins via α2-3/6 glycosidic linkages. Many enteric commensal and pathogenic bacteria can utilize sialic acids as a nutrient source, but not all express the sialidases that are required to release free sialic acid. Sialidases encoded by gut bacteria vary in terms of their substrate specificity and their enzymatic reaction. Most are hydrolytic sialidases, which release free sialic acid from sialylated substrates. However, there are also examples with transglycosylation activities. Recently, a third class of sialidases, intramolecular trans-sialidase (IT-sialidase), has been discovered in gut microbiota, releasing (2,7-anhydro-Neu5Ac) 2,7-anydro-N-acetylneuraminic acid instead of sialic acid. Reaction specificity varies, with hydrolytic sialidases demonstrating broad activity against α2,3-, α2,6- and α2,8-linked substrates, whereas IT-sialidases tend to be specific for α2,3-linked substrates. In this mini-review, we summarize the current knowledge on the structural and biochemical properties of sialidases involved in the interaction between gut bacteria and epithelial surfaces.

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“…By summing up these IFIEs calculated for individual fragments, overall binding energy between the ligand and protein can be estimated, which can be related to the resultant biological potency of the compound as measured in a biological assay. The correlated FMO calculation provides a complete list of interactions formed between the ligand and protein and so it is suitable for evaluating not only the electrostatic interactions (important in hydrogen-bonding) but also the van der Waals dispersion interactions (hydrophobic interactions) reliably and hence it has been successfully applied to study a lot of protein-ligand interactions by consistently evaluating their binding energies [17–21]. Recently, FMO calculations were made to study protein-peptide interactions to explain the experimental results [22].…”

Section: Introductionmentioning

confidence: 99%

Comparative Binding Analysis of Dipeptidyl Peptidase IV (DPP-4) with Antidiabetic Drugs – An Ab Initio Fragment Molecular Orbital Study

et al. 2016

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Dipeptidyl peptidase IV (DPP-4) enzyme is responsible for the degradation of incretins that stimulates insulin secretion and hence inhibition of DPP-4 becomes an established approach for the treatment of type 2 diabetics. We studied the interaction between DPP-4 and its inhibitor drugs (sitagliptin 1, linagliptin 2, alogliptin 3, and teneligliptin 4) quantitatively by using fragment molecular orbital calculations at the RI-MP2/cc-pVDZ level to analyze the inhibitory activities of the drugs. Apart from having common interactions with key residues, inhibitors encompassing the DPP-4 active site extensively interact widely with the hydrophobic pocket by their hydrophobic inhibitor moieties. The cumulative hydrophobic interaction becomes stronger for these inhibitors and hence linagliptin and teneligliptin have larger interaction energies, and consequently higher inhibitory activities, than their alogliptin and sitagliptin counterparts. Though effective interaction for both 2 and 3 is at subsite, 2 has a stronger binding to this subsite interacting with Trp629 and Tyr547 than 3 does. The presence of triazolopiperazine and piperazine moiety in 1 and 4, respectively, provides the interaction to the S2 extensive subsite; however, the latter’s superior inhibitory activity is not only due to a relatively tighter binding to the S2 extensive subsite, but also due to the interactions to the S1 subsite. The calculated hydrophobic interfragment interaction energies correlate well with the experimental binding affinities (KD) and inhibitory activities (IC50) of the DPP-4 inhibitors.

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Catalytic preference of Salmonella typhimurium LT2 sialidase for N‐acetylneuraminic acid residues over N‐glycolylneuraminic acid residues

Cited by 26 publications

References 38 publications

Streptococcus pneumoniae Senses a Human-like Sialic Acid Profile via the Response Regulator CiaR

Streptococcus pneumoniae Senses a Human-like Sialic Acid Profile via the Response Regulator CiaR

Sialidases from gut bacteria: a mini-review

Comparative Binding Analysis of Dipeptidyl Peptidase IV (DPP-4) with Antidiabetic Drugs – An Ab Initio Fragment Molecular Orbital Study

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