Local structural plasticity of the Staphylococcus aureus evasion protein EapH1 enables engagement with multiple neutrophil serine proteases.

ABSTRACT: Members of the EAP family of Staphylococcus aureus immune evasion proteins potently inhibit the neutrophil serine proteases (NSPs) neutrophil elastase, cathepsin-G, and proteinase-3. Previously, we determined a 1.8 Å resolution crystal structure of the EAP family member EapH1 bound to neutrophil elastase. This structure revealed that EapH1 blocks access to the enzyme's active site by forming a noncovalent complex with this host protease. To determine how EapH1 inhibits other NSPs, we studied here the effects of EapH1 on cathepsin-G. We found that EapH1 inhibits cathepsin-G with a K_i of 9.8 ± 4.7 nm Although this K_i value is ∼466-fold weaker than the K_i for EapH1 inhibition of neutrophil elastase, the time dependence of inhibition

SUBMITTER: Herdendorf TJ 

PROVIDER: S-EPMC7261791 | biostudies-literature | 2020 May

REPOSITORIES: biostudies-literature