Structural annotation of the conserved carbohydrate esterase vb_24B_21 from Shiga toxin-encoding bacteriophage Φ24B

Franke, Barbara; Veses-Garcia, Marta; Diederichs, Kay; Allison, Heather E.; Rigden, Daniel J.; Mayans, Olga

doi:10.1016/j.jsb.2020.107596

Cited by 4 publications

(2 citation statements)

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“…Diversity in the catalytic domain was mainly restricted to a few amino acid positions, but higher variability was detected for the C-terminal domain. Remarkably, a study on the crystal structure of the C-terminal domain of vb_24B_21 NanS-p from phage Φ24B [61] revealed a lectin-like, jelly-roll β-sandwich fold that predictably acts as a non-catalytic carbohydrate-binding module that could assist esterase activity. Further studies are necessary to evaluate if the NanS-p subtypes differ in their activity or in binding specificity.…”

Section: Discussionmentioning

confidence: 99%

Characterization of the flanking region of the Shiga toxin operon in Stx2a bacteriophages reveals a diversity of the NanS-p sialate O-acetylesterase gene

et al. 2023

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<abstract> Shiga toxin-producing <italic>E. coli</italic> (STEC) are diarrheagenic strains that can cause bloody diarrhea and hemolytic-uremic syndrome. Their main virulence factor, the Shiga toxin (Stx), is encoded by phages integrated into the bacterial chromosome. Stx phages are widely diverse and carry many genes with limited or unknown function. As the toxin subtype Stx2a is associated with highly pathogenic strains, this study was mainly focused on the characterization of the <italic>stx</italic> flanking region of Stx2a phages. Of particular interest was a sialate O-acetylesterase (NanS-p), which has been described previously to be encoded downstream <italic>stx</italic> in some phage genomes and may confer a growth advantage for STEC. Complete DNA sequences of Stx2a phages and prophages were retrieved from the GenBank database, and the genomic regions from anti-terminator Q to holin S genes were bioinformatically analyzed. Predicted NanSp sequences from phages encoding other Stx subtypes were also studied. Additionally, expression of <italic>nan</italic>S-p was quantified by qPCR in strains selected from our laboratory collection. The analysis of Stx2a phage genomes showed that all carried the <italic>Q</italic>, <italic>stx</italic>2a, <italic>nan</italic>S-p and <italic>S</italic> genes, but with allele diversity and other sequence differences. In particular, sequence differences were detected in each of the three domains of NanS-p esterases encoded by Stx2a phages and other Stx phages; however, <italic>nan</italic>S-p was not identified in the Stx2e, Stx2f and Stx2g phages analyzed. The expression of <italic>nan</italic>S-p increased in most <italic>stx</italic>2a-positive strains under phage inducing conditions, as was previously shown for <italic>stx</italic>2a. As the present work showed diversity at the Q-S region among Stx phages, and particularly in the encoded NanS-p enzyme, future studies will be necessary to evaluate if NanS-p variants differ in their activity and to assess the impact of the absence of <italic>nan</italic>S-p in certain Stx phages. </abstract>

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Section: Discussionmentioning

confidence: 99%

Characterization of the flanking region of the Shiga toxin operon in Stx2a bacteriophages reveals a diversity of the NanS-p sialate O-acetylesterase gene

et al. 2023

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“…• 3X2L (Nakamura et al, 2015) • 3X32 (Hirano et al, 2015) • 4TKJ (Matsuoka et al, 2015) • 3X0J (Furuike et al, 2016) • 5WQR (Ohno et al, 2017) • 6EQE (Austin et al, 2018) • 6ETK (Vergara et al, 2018) • 6FJN (Baker et al, 2019) • 6JGJ (Takaba et al, 2019) • 6RYG (Paterson et al, 2019) • 6IIP (Tian et al, 2019) • 6Q01 (Schellenberg et al, 2020) • 6XVM (Plaza-Garrido et al, 2020) • 6Y5S (Wu et al, 2020) • 6YP6 (Franke et al, 2020) • 7A5M (Barone et al, 2020) • 7K4T (Otten et al, 2020) • 6YK4 (Frydenvang et al, 2020) • 6SAY (Glöckner et al, 2020)…”

Section: A Geometric Algebramentioning

confidence: 99%

Geometric Algebra Attention Networks for Small Point Clouds

Spellings¹

2021

Preprint

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Much of the success of deep learning is drawn from building architectures that properly respect underlying symmetry and structure in the data on which they operate-a set of considerations that have been united under the banner of geometric deep learning. Often problems in the physical sciences deal with relatively small sets of points in two-or three-dimensional space wherein translation, rotation, and permutation equivariance are important or even vital for models to be useful in practice. In this work, we present rotation-and permutation-equivariant architectures for deep learning on these small point clouds, composed of a set of products of terms from the geometric algebra and reductions over those products using an attention mechanism. The geometric algebra provides valuable mathematical structure by which to combine vector, scalar, and other types of geometric inputs in a systematic way to account for rotation invariance or covariance, while attention yields a powerful way to impose permutation equivariance. We demonstrate the usefulness of these architectures by training models to solve sample problems relevant to physics, chemistry, and biology.

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The sialyl-O-acetylesterase NanS of Tannerella forsythia encompasses two catalytic modules with different regiospecificity for O7 and O9 of sialic acid

et al. 2021

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The periodontal pathogen Tannerella forsythia utilizes host sialic acids as a nutrient source. To also make O-acetylated sialyl residues susceptible to the action of its sialidase and sialic acid up-take system, Tannerella produces NanS, an O-acetylesterase with two putative catalytic domains. Here, we analyzed NanS by homology modeling, predicted a catalytic serine-histidine-aspartate triad for each catalytic domain and performed individual domain inactivation by single alanine exchanges of the triad nucleophiles S32 and S311. Subsequent functional analyses revealed that both domains possess sialyl-O-acetylesterase activity, but differ in their regioselectivity with respect to position O9 and O7 of sialic acid. The 7-O-acetylesterase activity inherent to the C-terminal domain of NanS is unique among sialyl-O-acetylesterases and fills the current gap in tools targeting 7-O-acetylation. Application of the O7-specific variant NanS-S32A allowed us to evidence the presence of cellular 7,9-di-O-acetylated sialoglycans by monitoring the gain in 9-O-acetylation upon selective removal of acetyl groups from O7. Moreover, we established de-7,9-O-acetylation by wild-type NanS as an easy and efficient method to validate the specific binding of three viral lectins commonly used for the recognition of (7),9-O-acetylated sialoglycans. Their binding critically depends on an acetyl group in O9, yet de-7,9-O-acetylation proved advantageous over de-9-O-acetylation as the additional removal of the 7-O-acetyl group eliminated ligand formation by 7,9-ester migration. Together, our data show that NanS gained dual functionality through recruitment of two esterase modules with complementary activities. This enables Tannerella to scavenge 7,9-di-O-acetylated sialyl residues and provides a novel, O7-specific tool for studying sialic acid O-acetylation.

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Structural annotation of the conserved carbohydrate esterase vb_24B_21 from Shiga toxin-encoding bacteriophage Φ24B

Cited by 4 publications

References 38 publications

Characterization of the flanking region of the Shiga toxin operon in Stx2a bacteriophages reveals a diversity of the NanS-p sialate O-acetylesterase gene

Characterization of the flanking region of the Shiga toxin operon in Stx2a bacteriophages reveals a diversity of the NanS-p sialate O-acetylesterase gene

Geometric Algebra Attention Networks for Small Point Clouds

The sialyl-O-acetylesterase NanS of Tannerella forsythia encompasses two catalytic modules with different regiospecificity for O7 and O9 of sialic acid

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