Molecular Basis of Calcium-Induced Acidic Shift in Antimicrobial Zinc Sequestration by S100A12.

ABSTRACT: Antimicrobial protein S100A12 sequesters Zn(II) via a His₃Asp motif to inhibit pathogens during infection. Here, UV-vis and NMR spectroscopies and molecular dynamics (MD) simulations are used to gain molecular insight into the Zn(II) chelation properties of S100A12 under pH conditions relevant to infection and inflammation. UV-vis measurements show that binding of Zn(II) to apo S100A12 exhibits a sigmoidal dependence with pH, beginning its decline at pH 7.0 and vanishing at pH 4.0. In the Ca(II)-bound protein, a similar sigmoidal curve is found to exhibit an acidic shift, an effect not attributed to a Ca(II)-induced pK_a suppression of the His₃Asp scaffold. NMR measurements show that upon lowering the pH, resonances exhibit nonlinear migration trends

SUBMITTER: Kothalawala M 

PROVIDER: S-EPMC12498495 | biostudies-literature | 2025 Oct

REPOSITORIES: biostudies-literature