Influence of nonenzymatic posttranslational modifications on constitution, oligomerization and receptor binding of S100A12

Augner K, Eichler J, Utz W, Pischetsrieder M (2014)

Publication Type: Journal article

Publication year: 2014

Journal

PLoS ONE Public Library of Science

Publisher: Public Library of Science

Book Volume: 9

Pages Range: e113418

Journal Issue: 11

URI: http://dx.plos.org/10.1371/journal.pone.0113418

DOI: 10.1371/journal.pone.0113418

Abstract

This study examined the effect of methylglyoxal (MGO)-derived nonenzymatic posttranslational modifications (nePTMs) on the binding affinity of S100A12 to its natural receptor for advanced glycation end-products (RAGE). Binding of MGOmodified S100A12 to RAGE decreased significantly with increasing MGO concentration and incubation time. Ca²⁺-induced S100A12 hexamerization was impaired only at higher MGO concentrations indicating that the loss of affinity is not predominantly caused by disturbance of ligand oligomerization. nePTM mapping showed carboxyethylation of lysine (CEL) and the N-terminus without preferential modification sites. Besides, hydroimidazolone, hemiaminals, argpyrimidine, and tetrahydropyrimidine rapidly formed at R21. Even at the highest modification rate, hexamerization of synthesized CEL-S100A12 was unaffected and RAGE-binding only slightly impaired. Thus, nePTMs at R21 seem to be the major cause of MGOinduced impairment of S100A12 oligomerization and RAGE binding.

Authors with CRIS profile

Kerstin Augner Lehrstuhl für Lebensmittelchemie (Henriette-Schmidt-Burkhardt Lehrstuhl) Jutta Eichler Professur für Pharmazeutische Chemie Wolfgang Utz Lehrstuhl für Lebensmittelchemie (Henriette-Schmidt-Burkhardt Lehrstuhl) Monika Pischetsrieder Lehrstuhl für Lebensmittelchemie (Henriette-Schmidt-Burkhardt Lehrstuhl)

Additional Organisation(s)

Emil-Fischer-Zentrum (Emil Fischer Center)

How to cite

APA:

Augner, K., Eichler, J., Utz, W., & Pischetsrieder, M. (2014). Influence of nonenzymatic posttranslational modifications on constitution, oligomerization and receptor binding of S100A12. PLoS ONE, 9(11), e113418. https://doi.org/10.1371/journal.pone.0113418

MLA:

Augner, Kerstin, et al. "Influence of nonenzymatic posttranslational modifications on constitution, oligomerization and receptor binding of S100A12." PLoS ONE 9.11 (2014): e113418.

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