38 Bacterial Teichoic Acid Binding by Solid-State NMR

Wednesday, November 4, 2009
Ballroom A+B (Camino Real Hotel)
Jeffrey L. Halye , Department of Chemistry and Biochemistry, University of Oklahoma, Norman, OK
Charles V. Rice , Department of Chemistry and Biochemistry, The University of Oklahoma, Norman, OK
Bacteria use teichoic acid to bind metals and repel antimicrobial peptides; yet the proposed chemical mechanisms remain untested. An effective means of studying these mechanisms in biological systems is through cadmium NMR. This technique has proven effective in probing the interaction between biomolecules, such as proteins and peptides, with divalent metals, such as zinc, copper, magnesium or calcium. Gram-positive bacteria, such as S. aureus and B. subtilis, have peptidoglycan cell walls which contain teichoic acids, a poly(phosphodiester) biopolymer used for, among other things, metal chelation. Additionally, D-Alanine, found as a side-chain attached to the beta-carbon of teichoic acid phosphodiester, binds via the C-terminus, thereby allowing the amine to exist as a free cationic NH3+ group with the ability to form a contact-ion-pair with the nearby anionic phosphate group. Rotational-echo double-resonance (REDOR) NMR spectroscopy has been used to determine that 1) teichoic acid phosphoryl groups bind metals at low concentrations in a monodentate bridging conformation with internuclear distances of ~4.15 and ~4.90 and, 2) binding of divalent metal ions causes an increase in the D-Alanine amine-to-phosphate distance from ~4.4 to ~5.4 . These results show that although metal ions interact with phosphoryl binding sites through solvent-separated ion-pairing, these metals at typical environmental concentrations still play an important role in the neutralization of the bulk negative charge associated with the phosphodiester backbone of teichoic acid. This, in turn, allows the now labile D-Alanine side-chains to repel cationic antimicrobial peptides (CAMPs) through Coulombic repulsion via the cationic amine. Additionally, the amine of D-Ala does not prevent divalent cation chelation in contradiction to the prevailing view of teichoic acids in metal binding. Thus, the NMR-based description of the teichoic acid structure advances the basic understanding of cell wall biochemistry and provides possible insight into the creation of new antibiotic therapies.
See more of: Wednesday Poster Session
See more of: Abstract Submission