Cystatin A
Cystatin-A is a protein that in humans is encoded by the CSTA gene.
The cystatin superfamily encompasses proteins that contain multiple cystatin-like sequences. Some of the members are active cysteine protease inhibitors, while others have lost or perhaps never acquired this inhibitory activity. There are three inhibitory families in the superfamily, including the type 1 cystatins, type 2 cystatins, and kininogens. This gene encodes a stefin that functions as a cysteine protease inhibitor, forming tight complexes with papain and the cathepsins B, H, and L. The protein is one of the precursor proteins of cornified cell envelope in keratinocytes and plays a role in epidermal development and maintenance. Stefins have been proposed as prognostic and diagnostic tools for cancer.
Structure and inhibatory mechanism
The structure of cystatin A features a wedge-like shape that's typical of cysteine protease inhibitors. This shape is critical for how it blocks protease activity. The protein has three main functional regions:- An N-terminal region with a conserved glycine
- Two β-hairpin loops
- A C-terminal region that helps stabilize the structure
- Leu73 in the second binding loop plays a crucial role in the inhibitory activity
- The N-terminal domain contributes about 40% of the overall binding energy
- Pro-3 and Ile-2 are particularly important for energy binding
Function
In tissues, cystatin A helps regulate protein breakdown by controlling the activity of these proteases. This regulation is important for normal cell function and can be disrupted in certain diseases.