Staphylococcus aureus evasion proteins EapH1 and EapH2: Residue-level investigation of an alternative binding motif for human neutrophil elastase.

ABSTRACT: The Staphylococcus aureusExtracellular Adherence Protein (Eap) and its homologs, EapH1 and EapH2, are a family of secreted proteins that potently inhibit the neutrophil serine proteases Neutrophil Elastase (hNE), Cathepsin G, and Proteinase 3. Similarly to EapH1, inhibition of hNE by EapH2 is characterized by a rapid association rate (2.9 × 10⁵ M^-1s^-1) coupled with a very slow dissociation rate (5.9 × 10^-4 s^-1), yielding an apparent inhibition constant of 2.11 nM. As with EapH1, inhibition of hNE by EapH2 is also time-dependent in character. A phenylalanine in EapH2 replaces the leucine in EapH1 that sits over the hNE catalytic serine and creates a potential steric clash. Indeed, the EapH1 L59F mutant is severely decreased in its abili

SUBMITTER: Herdendorf TJ 

PROVIDER: S-EPMC6938032 | biostudies-literature | 2019 Nov

REPOSITORIES: biostudies-literature