GZMH Human
Description
GZMH is fused to a 21 amino acid His-tag at N-terminus & purified by proprietary chromatographic techniques.
Product Specs
The N-terminus of GZMH is fused with a 21 amino acid His-tag to facilitate purification, which is achieved using proprietary chromatographic methods.
To ensure optimal protein stability during long-term storage, the addition of a carrier protein such as HSA or BSA at a concentration of 0.1% is advised.
Repeated freezing and thawing of the protein should be avoided.
Product Science Overview
Granzyme H is a chymotrypsin-like serine protease, meaning it has a similar structure and function to the digestive enzyme chymotrypsin . It is constitutively expressed in human NK cells, which are essential components of the innate immune system . The enzyme’s substrate preference and mechanism of substrate recognition are not fully understood, but it is known to have a preference for bulky, aromatic residues such as tyrosine and phenylalanine at the P1 position .
Granzyme H induces an alternative, caspase-independent cell-death program . Unlike other granzymes, such as granzyme B (GzmB), which activate caspases to induce apoptosis, granzyme H triggers cell death through a different pathway. This involves mitochondrial depolarization, reactive oxygen species (ROS) generation, DNA degradation, and chromatin condensation . The high expression levels of granzyme H in naive NK cells and its potent killing ability support its role in triggering an alternative cell-death pathway in innate immunity .
Research into granzyme H has provided structural insights into its substrate specificity and functional roles. For example, the crystal structures of a D102N-GzmH mutant alone and in complex with a decapeptide substrate and an inhibitor have been solved . These studies have revealed that an unusual RKR motif (Arg 39 -Lys 40 -Arg 41), conserved only in GzmH, helps define the S3′ and S4′ binding regions, indicating a preference for acidic residues at the P3′ and P4′ sites . Disruption of this motif or the acidic P3′ and P4′ residues in the substrate abolishes the proteolytic activity of GzmH .
Additionally, a tetrapeptide chloromethylketone inhibitor, Ac-PTSY-chloromethylketone, has been designed to selectively and efficiently block the enzymatic and cytotoxic activity of GzmH . This inhibitor provides a useful tool for further studies on the function of GzmH and its potential therapeutic applications.
