Substrate inhibition and allosteric regulation by heparan sulfate of Trypanosoma brucei cathepsin L

► Brucipain/rhodesain undergoes substrate inhibition by allostery. ► Suceptibility to substrate inhibiton is regulated by temperature. ► Enzyme conformational changes regulate suceptibility to substrate inhibiton. ► Heparan sulfate prevents substrate inhibition through interaction with the enzyme. ► Enzyme downmodulation via allostery prevents fibrinogen degradation.