Scientific Publications by FDA Staff
J Am Chem Soc 2012 Jul 4;134(26):10717-20
Evidence for helical structure in a tetramer of alpha2-8 sialic acid: unveiling a structural antigen.
Battistel MD, Shangold M, Trinh L, Shiloach J, Freedberg DI
Characteristic H-bonding patterns define secondary structure in proteins and nucleic acids. We show that similar patterns apply for a2-8 sialic acid (SiA) in H(2)O and that H-bonds define its structure. A (15)N,(13)C a2-8 SiA tetramer, (SiA)(4), was used as a model system for the polymer. At 263 K, we detected intra-residue through-H-bond J couplings between (15)N and C8 for residues R-I-R-III of the tetramer, indicating H-bonds between the (15)N's and the O8's of these residues. Additional J couplings between the (15)N's and C2's of the adjacent residues confirm the putative H-bonds. NH groups showing this long-range correlation also experience slower (1)H/(2)H exchange. Additionally, detection of couplings between H7 and C2 for R-II and R-III implies that the conformations of the linkers between these residues are different than in the monomers. These structural elements are consistent with two left-handed helical models: 2 residues/turn (2(4) helix) and 4 residues/turn (1(4) helix). To discriminate between models, we resorted to (1)H,(1)H NOEs. The 2(4) helical model is in better agreement with the experimental data. We provide direct evidence of H-bonding for (SiA)(4) and show how H-bonds can be a determining factor for shaping its 3D structure.
|Category: Journal Article|
|PubMed ID: #22703338||DOI: 10.1021/ja300624j|
|Includes FDA Authors from Scientific Area(s): Biologics|
|Entry Created: 2012-01-12||Entry Last Modified: 2015-08-24|