Abstract
The Streptococcal C5a peptidase (ScpA) specifically inactivates the human complement factor hC5a, a potent anaphylatoxin recently identified as a therapeutic target for treatment of COVID-19 infections. Engineering of ScpA to enhance its potential as a therapeutic will require detailed examination of the basis for its highly selective activity. The emerging view of ScpA and related subtilases is that selection of their substrates is a dynamic two-step process involving flexibility in the domains around the active site and in the C-ter of the substrate. Surface plasmon resonance (SPR) analyses of the ScpA-hC5a interaction have shown that high affinity binding of the substrate is driven by electrostatic interactions between an exosite on the Fn2 domain of the enzyme and the bulky N-ter cleavage product (P(N), 'core' residues 1-67) of C5a [1]. Introduction of a D783A mutation in the Fn2 exosite, located approximately 50 Å from the catalytic serine, was shown to significantly reduce substrate binding affinity and k (cat) of the enzyme. X-ray crystallographic studies on the D783A mutant (ScpA(D783A)) were undertaken to better interpret the impact of this mutation on the specificity and activity of ScpA. Here we present the 1.9 Å X-ray diffraction data for ScpA(D783A) and the molecular replacement solution for the structure. Both raw diffraction images and coordinates have been made available on public databases. Additional details on the related SPR and enzyme kinetics analyses on ScpA(D783A) reported in Jain et al. [2].