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Generalities

The ASP protein is a serine protease that will cut peptide bonds after specific amino acids. The kexin-like serine protease belongs to the subtilisin family (subtilases). The structure of ASP is similar to that of Kex2 ^[1], a protease of the subtilisin family, but ASP has a unique extra occluding region close to its active site.

The maturation of ASP is achieved by ORF2. This protein plays the role of an external chaperone and is necessary for the construction of the stable ASP. Indeed, ASP doesn’t contain a propeptide (such as Kex2) that is involved in the proper folding of the protein.

Secondary structure

Domains

The ASP protein contains an N-terminal region that forms the subtilisin domain and a C-terminal region that forms the P-domain. The subtilisin domain is composed of ten helices and twelve chains and goes from Gly3 to Pro341. The structure of the P-domain is a jelly roll-like fold with eight beta-strands. It extends from Leu432 to His595.

Insert figure of the domains.

The structure contains calcium ions. They are important because ...

Active site

The catalytic triad of ASP is composed of Asp78, His115 and Ser336. These amino acids are the base is the active site of the protein, where the mode of action of the serine protease takes place.

A peptide can be inserted in the space of the active site. There, the amino acids of the catalytic triad will interact together and the mechanism will lead to a cut in the polypeptide.

The mechanism is the following: The histidine will react with the Serine and deprotonate it. The deprotonated hydroxyl group of the serine will act as a nucleophilic species and attack the carbon from the carbonyl function on the peptide. This will lead to the formation of a tetrahedral intermediate. At the end, the regeneration of the active site will be done with the release of the peptide cut in two parts.

Disease

Relevance

Structural highlights

This is a sample scene created with SAT to by Group, and another to make of the protein. You can make your own scenes on SAT starting from scratch or loading and editing one of these sample scenes.