Mapping the binding site of C1-inhibitor for polyanion cofactors

•C1-inhibitor plays a vital anti-inflammatory role in the body by controlling pro-inflammatory pathways such as complement and coagulation.•The inhibitor’s action is enhanced in the presence of polyanionic cofactors, such as heparin and polyphosphate•Co factor binding site of the serpin was mapped and shown to be vital for rate enhancement•Findings provide new insight into the mechanism of interaction of co factors with C1-inhibitor.