The 1.25 Å resolution refinement of the cholera toxin B-pentamer: evidence of peptide backbone strain at the receptor-binding site

Merritt, E.A.; Kühn, Peter; Sarfaty, Steve; Erbe, Jarrod L.; Holmes, Randall K.; Hól, Wim G. J.

doi:10.1006/jmbi.1998.2076

Cited by 167 publications

(153 citation statements)

References 35 publications

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“…The crystal structure of CTB shows the pentamer to have a diameter of 6.5 nm and a depth of 3.5 nm. [24] These measurements are consistent with the experimental hydrodynamic diameter of 5.6 nm. At a 1:1 ratio of CTB and W88E(GM1), DLS showed a single peak at 8.4 nm.…”

supporting

confidence: 87%

“…The resulting neoglycoprotein has ligand groups arranged with optimal spacing to bind to the cholera toxin protein. In the 3D structure of CTB (PDB code: 3CHB), [24] the binding sites are marked in white, and N-terminal threonine residues are marked with black arrows. observed, which is consistent with a binding model in which W88E(GM1) forms a protein heterodimer complex with CTB.…”

mentioning

confidence: 99%

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A Protein‐Based Pentavalent Inhibitor of the Cholera Toxin B‐Subunit

et al. 2014

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Protein toxins produced by bacteria are the cause of many life-threatening diarrheal diseases. Many of these toxins, including cholera toxin (CT), enter the cell by first binding to glycolipids in the cell membrane. Inhibiting these multivalent protein/carbohydrate interactions would prevent the toxin from entering cells and causing diarrhea. Here we demonstrate that the site-specific modification of a protein scaffold, which is perfectly matched in both size and valency to the target toxin, provides a convenient route to an effective multivalent inhibitor. The resulting pentavalent neoglycoprotein displays an inhibition potency (IC 50 ) of 104 pm for the CT B-subunit (CTB), which is the most potent pentavalent inhibitor for this target reported thus far. Complexation of the inhibitor and CTB resulted in a protein heterodimer. This inhibition strategy can potentially be applied to many multivalent receptors and also opens up new possibilities for protein assembly strategies.

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supporting

confidence: 87%

mentioning

confidence: 99%

A Protein‐Based Pentavalent Inhibitor of the Cholera Toxin B‐Subunit

et al. 2014

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“…A further structural constraint imposed by the branch point in GT1b is rotation about the GalNAc␤ (1,4)Gal bond. A search of GalNAc␤-(1,4)Gal␤ torsion angles using the GlyTorsion tool at CSS (44) yielded 13 linkages (from 5 PDB entries, 3CHB, 2CHB, 1CT1, 1FV3, 1FV2, representing 2 unique proteins/ligands, cholera toxin/GM1 and tetanus toxin/GT1b-b analog (45)(46)(47)). All contain the branch-point GalNAc␤(1,4)[Neu5Ac␣(2,3)]Gal␤ and share angles in the -ac/-sc region (Table 3).…”

Section: Sugar Linkage Dihedral Angle (°); Stereochemical Arrangementmentioning

confidence: 99%

Siglec-7 Undergoes a Major Conformational Change When Complexed with the α(2,8)-Disialylganglioside GT1b

Attrill

Imamura

Sharma

et al. 2006

Journal of Biological Chemistry

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The siglecs are a group of mammalian sialic acid binding receptors expressed predominantly in the immune system. The CD33-related siglecs show complex recognition patterns for sialylated glycans. Siglec-7 shows a preference for ␣(2,8)-disialylated ligands and provides a structural template for studying the key interactions that drive this selectivity. We have co-crystallized Siglec-7 with a synthetic oligosaccharide corresponding to the ␣(2,8)-disialylated ganglioside GT1b. The crystal structure of the complex offers a first glimpse into how this important family of lectins binds the structurally diverse gangliosides. The structure reveals that the C-C loop, a region implicated in previous studies as driving siglec specificity, undergoes a dramatic conformational shift, allowing it to interact with the underlying neutral glycan core of the ganglioside. The structural data in combination with mutagenesis studies show that binding of the ganglioside is driven by extensive hydrophobic contacts together with key polar interactions and that the binding site structure is complementary to preferred solution conformations of GT1b.

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“…5). The second is the cholera toxin B-pentamer re®ned at 1.25 A Ê (Merritt et al, 1998; PDB code 3chb), which contains ®ve crystallographically independent copies of the toxin's 103-residue B subunit. The third case is the 1.14 A Ê re®nement of a streptavidin mutant (Freitag et al, 1999; PDB code 1swu), which contains four crystallographically independent subunits per asymmetric unit.…”

Section: Non-crystallographic Symmetrymentioning

confidence: 99%

“…Mean similarity in anisotropy S uij per residue in pairwise comparisons of monomers in the cholera toxin B-pentamer (Merritt et al, 1998; PDB code 3chb). The ®ve monomer chains, identi®ed D through H, are related by ®vefold non-crystallographic symmetry; the r.m.s.…”

Section: Figurementioning

confidence: 99%

Comparing anisotropic displacement parameters in protein structures

Merritt

1999

Acta Crystallogr D Biol Crystallogr

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The increasingly widespread use of synchrotron-radiation sources and cryo-preparation of samples in macromolecular crystallography has led to a dramatic increase in the number of macromolecular structures determined at atomic or near-atomic resolution. This permits expansion of the structural model to include anisotropic displacement parameters Uij for individual atoms. In order to explore the physical significance of these parameters in protein structures, it is useful to be able to compare quantitatively the electron-density distribution described by the refined Uij values associated with corresponding crystallographically independent atoms. This paper presents the derivation of an easily calculated correlation coefficient in real space between two atoms modeled with anisotropic displacement parameters. This measure is used to investigate the degree of similarity between chemically equivalent but crystallographically independent atoms in the set of protein structural models currently available from the Protein Data Bank.

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The 1.25 Å resolution refinement of the cholera toxin B-pentamer: evidence of peptide backbone strain at the receptor-binding site

Cited by 167 publications

References 35 publications

A Protein‐Based Pentavalent Inhibitor of the Cholera Toxin B‐Subunit

A Protein‐Based Pentavalent Inhibitor of the Cholera Toxin B‐Subunit

Siglec-7 Undergoes a Major Conformational Change When Complexed with the α(2,8)-Disialylganglioside GT1b

Comparing anisotropic displacement parameters in protein structures

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