6y54

From Proteopedia

(Difference between revisions)

Current revision

Crystal structure of a Neisseria meningitidis serogroup A capsular oligosaccharide bound to a functional Fab

Structural highlights

6y54 is a 6 chain structure with sequence from Mus musculus. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Method:	X-ray diffraction, Resolution 2.67Å
Ligands:	, , , ,
Resources:	FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Publication Abstract from PubMed

Meningococcal meningitis remains a substantial cause of mortality and morbidity worldwide. Until recently, countries in the African meningitis belt were susceptible to devastating outbreaks, largely attributed to serogroup A Neisseria meningitidis (MenA). Vaccination with glycoconjugates of MenA capsular polysaccharide led to an almost complete elimination of MenA clinical cases. To understand the molecular basis of vaccine-induced protection, we generated a panel of oligosaccharide fragments of different lengths and tested them with polyclonal and monoclonal antibodies by inhibition enzyme-linked immunosorbent assay, surface plasmon resonance, and competitive human serum bactericidal assay, which is a surrogate for protection. The epitope was shown to optimize between three and six repeating units and to be O-acetylated. The molecular interactions between a protective monoclonal antibody and a MenA capsular polysaccharide fragment were further elucidated at the atomic level by saturation transfer difference NMR spectroscopy and X-ray crystallography. The epitope consists of a trisaccharide anchored to the antibody via the O- and N-acetyl moieties through either H-bonding or CH-pi interactions. In silico docking showed that 3-O-acetylation of the upstream residue is essential for antibody binding, while O-acetate could be equally accommodated at three and four positions of the other two residues. These results shed light on the mechanism of action of current MenA vaccines and provide a foundation for the rational design of improved therapies.

Structure of a protective epitope reveals the importance of acetylation of Neisseria meningitidis serogroup A capsular polysaccharide.,Henriques P, Dello Iacono L, Gimeno A, Biolchi A, Romano MR, Arda A, Bernardes GJL, Jimenez-Barbero J, Berti F, Rappuoli R, Adamo R Proc Natl Acad Sci U S A. 2020 Nov 6. pii: 2011385117. doi:, 10.1073/pnas.2011385117. PMID:33158970^[1]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

References

↑ Henriques P, Dello Iacono L, Gimeno A, Biolchi A, Romano MR, Arda A, Bernardes GJL, Jimenez-Barbero J, Berti F, Rappuoli R, Adamo R. Structure of a protective epitope reveals the importance of acetylation of Neisseria meningitidis serogroup A capsular polysaccharide. Proc Natl Acad Sci U S A. 2020 Nov 24;117(47):29795-29802. PMID:33158970 doi:10.1073/pnas.2011385117

1 Structural highlights
2 Publication Abstract from PubMed
3 See Also
4 References

Proteopedia Page Contributors and Editors (what is this?)

OCA

Retrieved from "http://52.214.119.220/wiki/index.php/6y54"

Categories: Large Structures | Mus musculus | Adamo R | Dello Iacono L | Henriques P

@@ Line 5: / Line 5: @@
 <table><tr><td colspan='2'>[[6y54]] is a 6 chain structure with sequence from [https://en.wikipedia.org/wiki/Mus_musculus Mus musculus]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6Y54 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=6Y54 FirstGlance]. <br>
 </td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 2.67&#8491;</td></tr>
-<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=EDO:1,2-ETHANEDIOL'>EDO</scene>, <scene name='pdbligand=IOD:IODIDE+ION'>IOD</scene>, <scene name='pdbligand=OA8:{[(2R,3S,4R,5S,6S)-3-(acetyloxy)-5-acetamido-4,6-dihydroxyoxan-2-yl]methoxy}phosphonic+acid'>OA8</scene>, <scene name='pdbligand=OAB:{[(2R,3S,4R,5S,6S)-5-acetamido-3,6-dihydroxy-4-(2-oxopropyl)oxan-2-yl]methoxy}phosphonic+acid'>OAB</scene>, <scene name='pdbligand=OOW:{[(2R,3S,4R,5S,6R)-5-acetamido-3-hydroxy-4-(2-oxopropyl)-6-(phosphonooxy)oxan-2-yl]methoxy}phosphonic+acid'>OOW</scene></td></tr>
+<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=EDO:1,2-ETHANEDIOL'>EDO</scene>, <scene name='pdbligand=IOD:IODIDE+ION'>IOD</scene>, <scene name='pdbligand=OA8:[(2~{R},3~{S},4~{R},5~{S})-5-acetamido-4,6-bis(oxidanyl)-2-(phosphonooxymethyl)oxan-3-yl]+ethanoate'>OA8</scene>, <scene name='pdbligand=OAB:[(3~{S},4~{R},5~{S},6~{R})-3-acetamido-2,5-bis(oxidanyl)-6-(phosphonooxymethyl)oxan-4-yl]+ethanoate'>OAB</scene>, <scene name='pdbligand=OOW:[(2~{R},3~{S},4~{R},5~{S},6~{R})-3-acetamido-5-oxidanyl-2-phosphonooxy-6-(phosphonooxymethyl)oxan-4-yl]+ethanoate'>OOW</scene></td></tr>
 <tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=6y54 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6y54 OCA], [https://pdbe.org/6y54 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=6y54 RCSB], [https://www.ebi.ac.uk/pdbsum/6y54 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=6y54 ProSAT]</span></td></tr>
 </table>

6y54

From Proteopedia

Current revision

Crystal structure of a Neisseria meningitidis serogroup A capsular oligosaccharide bound to a functional Fab

Structural highlights

Publication Abstract from PubMed

See Also

References

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