Conformational analysis of diribosylribitol phosphate by NMR spectroscopy and molecular dynamics

Maestre, M.; Pérez, Carolina

doi:10.1002/(sici)1097-458x(200002)38:2<123::aid-mrc586>3.0.co;2-l

Cited by 2 publications

(2 citation statements)

References 10 publications

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“…The conformation of the Hib antigen in solution has been previously widely investigated, particularly through the application of NMR and molecular dynamics (MD) simulations. Indeed, earlier studies already highlighted the remarkable flexibility of the OS chains. − As already mentioned, from the NMR analysis, it can be assessed that both DP2 and DP3 are fairly flexible molecules in solution with high conformational mobility along the torsional degrees of freedom at the linear ribitol chains, together with the pseudorotation at the five-membered ribose rings. However, once bound to the CA4 antibody, they adopt a well-defined conformation, in which the ribitol chain is perfectly accommodated into the antibody-binding pocket and the ribose ring displays a precise ring shape.…”

Section: Discussionmentioning

confidence: 94%

A Multidisciplinary Structural Approach to the Identification of the Haemophilus influenzae Type b Capsular Polysaccharide Protective Epitope

Nonne,

Iacono,

Bertuzzi

et al. 2024

ACS Cent. Sci.

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Glycoconjugate vaccines so far licensed are generally composed of a native or size-reduced capsular polysaccharide conjugated to carrier proteins. Detailed information on the structural requirements necessary for CPS recognition is becoming the key to accelerating the development of next-generation improved glycoconjugate vaccines. Structural glycobiology studies using oligosaccharides (OS) complexed with functional monoclonal antibodies represent a powerful tool for gaining information on CPS immunological determinants at the atomic level. Herein, the minimal structural epitope of Haemophilus influenzae type b (Hib) CPS recognized by a functional human monoclonal antibody (hmAb) is reported. Short and well-defined Hib oligosaccharides originating from the depolymerization of the native CPS have been used to elucidate saccharide−mAb interactions by using a multidisciplinary approach combining surface plasmon resonance (SPR), saturation transfer differencenanomagnetic resonance (STD-NMR), and X-ray crystallography. Our study demonstrates that the minimal structural epitope of Hib is comprised within two repeating units (RUs) where ribose and ribitol are directly engaged in the hmAb interaction, and the binding pocket fully accommodates two RUs without any additional involvement of a third one. Understanding saccharide antigen structural characteristics can provide the basis for the design of innovative glycoconjugate vaccines based on alternative technologies, such as synthetic or enzymatic approaches.

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Section: Discussionmentioning

confidence: 94%

A Multidisciplinary Structural Approach to the Identification of the Haemophilus influenzae Type b Capsular Polysaccharide Protective Epitope

Nonne,

Iacono,

Bertuzzi

et al. 2024

ACS Cent. Sci.

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“…Good agreement was found between NMR observables and the MD simulation which used the GROMOS force field. 24 III. Solvent Structure.…”

Section: Resultsmentioning

confidence: 99%

Molecular Dynamics Simulations of the Phosphodiester-Linked Repeating Units of the Haemophilus influenzae Types c and f Capsular Polysaccharides

2001

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The three-dimensional structure of the repeating units of Haemophilus influenzae types c and f capsular polysaccharides (CPS) have been investigated by molecular dynamics simulations. The models consist of disaccharides joined by phosphodiester linkages, explicit water, and sodium as the counterion. Four 1 ns simulations were performed for each type, with either different starting conformations or different methods to handle long-range truncation effects, namely, Ewald summation or force shift truncation. For the average properties investigated, the choice of the method did not make any significant difference. Limited flexibility was observed close to the sugar residues, whereas at the phosphorus atom, the torsions showed major transitions. For comparison, 3 J H,P was measured on CPS material. On the basis of these spin-spin couplings, only small changes are required in the models of the disaccharide repeating unit to agree with data on the CPS. In addition, hydrogen bonding and radial and spatial distribution functions were analyzed to obtain a picture of solvent ordering around the disaccharides.

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Conformational analysis of diribosylribitol phosphate by NMR spectroscopy and molecular dynamics

Cited by 2 publications

References 10 publications

A Multidisciplinary Structural Approach to the Identification of the Haemophilus influenzae Type b Capsular Polysaccharide Protective Epitope

A Multidisciplinary Structural Approach to the Identification of the Haemophilus influenzae Type b Capsular Polysaccharide Protective Epitope

Molecular Dynamics Simulations of the Phosphodiester-Linked Repeating Units of the Haemophilus influenzae Types c and f Capsular Polysaccharides

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