The protease associated (PA) domain in ScpA from Streptococcus pyogenes plays a role in substrate recruitment.
Biochim Biophys Acta Proteins Proteom
; 1871(6): 140946, 2023 11 01.
Article
em En
| MEDLINE
| ID: mdl-37562488
ABSTRACT
Annually, over 18 million disease cases and half a million deaths worldwide are estimated to be caused by Group A Streptococcus. ScpA (or C5a peptidase) is a well characterised member of the cell enveleope protease family, which possess a S8 subtilisin-like catalytic domain and a shared multi-domain architecture. ScpA cleaves complement factors C5a and C3a, impairing the function of these critical anaphylatoxins and disrupts complement-mediated innate immunity. Although the high resolution structure of ScpA is known, the details of how it recognises its substrate are only just emerging. Previous studies have identified a distant exosite on the 2nd fibronectin domain that plays an important role in recruitment via an interaction with the substrate core. Here, using a combination of solution NMR spectroscopy, mutagenesis with functional assays and computational approaches we identify a second exosite within the protease-associated (PA) domain. We propose a model in which the PA domain assists optimal delivery of the substrate's C terminus to the active site for cleavage.
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Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
Peptídeo Hidrolases
/
Streptococcus pyogenes
Tipo de estudo:
Prognostic_studies
/
Risk_factors_studies
Idioma:
En
Revista:
Biochim Biophys Acta Proteins Proteom
Ano de publicação:
2023
Tipo de documento:
Article
País de afiliação:
Reino Unido