Structural requirements for cathepsin B and cathepsin H inhibition by kininogens

Abstract

Domain 3 (D3) of human kininogens, the major cysteine proteinase inhibitors in plasma, has been shown to be the tightest binding inhibitory domain for cathepsins B and H. D3 was expressed in three fragments as its exon products as follows: exon 7 (Gly235-Gln292), exon 8 (Gln292-Gly328), and exon 9 (Gln329-Met357). Exon products 7, 8, and 9 alone as well as exon product 7 + 9 each exhibited an 1C50 value 5- to 30-fold higher (5-30 microM) than exon products 7 + 8 and 8 + 9 (0.9-1.3 microM) for cathepsins B and H, respectively. However, in turn, the exon products 7 + 8 and 8 + 9 seemed to be less potent inhibitors than the intact D3 (10, 200 nM) or HK (200, 500 nM) molecule. These results clearly indicate that an intact molecule of HK or its domain 3 as a whole is required for optimal inhibition of cathepsins B and H.

Plant protein and vegetable oil-based diets modulate gilthead seabream (Sparus aurata) muscle biochemical status and proteolytic enzymes at an early postmortem stage

“…On the other hand, Panserat et al (2008), in a study focusing on hepatic genomic profiles of rainbow trout fed with plant proteins or vegetable oils, has found that the use of a blend of vegetable oils in the diets resulted in a decrease in expression of the cathepsin B gene in the liver, while the use of vegetable proteins had no effect on this gene. The lower cathepsin B activity observed in the present study could be a result of inactivation due to oxidative processes (Bano et al 1996). We found no evidence of increased oxidation in seabream fed the PPVO diet at such an early postmortem stage.…”

“…The lower cathepsin B activity observed in the present study could be a result of inactivation due to oxidative processes (Bano et al . ). We found no evidence of increased oxidation in seabream fed the PPVO diet at such an early postmortem stage.…”

Effect of harvesting stress and storage conditions on protein degradation in fillets of farmed gilthead seabream (Sparus aurata): A differential scanning calorimetry study

“…Even if some lysosome rupture occurred during ice-storage, it is likely that cathepsin B was not inactivated due to autolysis during the storage period (Cheret et al, 2006). On the other hand, it is possible that cathepsin B was irreversibly inactivated during frozen storage, due to oxidation of the cysteine residues (Bano, Kunapuli, Bradford, & Colman, 1996). Thiol-dependent proteases such as cathepsin B are prone to inactivation by a wide range of amino acid, peptide and protein hydroperoxides (Headlam, Gracanin, Rodgers, & Davies, 2006).…”

Human Plasma Kallikrein-Kinin System: Physiological and Biochemical Parameters

“…Domain 3, like domain 5, has platelet- neutrophil- and endothelial cell-binding action [12,12–15]. Intact HK, but not the oxidized HK or its domain 3, is an inhibitor of cathepsin B and H[16,17]. …”