Cystatin A

From Wikipedia, the free encyclopedia

Template:Short description Template:Cs1 config An Error has occurred retrieving Wikidata item for infobox Cystatin-A is a protein that in humans is encoded by the CSTA gene.[1][2]

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 (stefins), 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.[2]

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.[3] The protein has three main functional regions:

  • An N-terminal region with a conserved glycine[3]
  • Two β-hairpin loops (the first loop contains the important QVVAG sequence shown in blue in the image)[3]
  • A C-terminal region that helps stabilize the structure[3]

These three regions work together to form the functional core that fits into the catalytic cleft of target proteases. The inhibitory mechanism depends on specific structural features:

  • Leu73 in the second binding loop plays a crucial role in the inhibitory activity[4]
  • The N-terminal domain contributes about 40% of the overall binding energy[5]
  • Pro-3 and Ile-2 are particularly important for energy binding[5]

Function

Cystatin A mainly works as an inhibitor of cysteine proteases, with strong binding to papain and cathepsins B, H, and L. It also serves as a building block for the cornified cell envelope in skin cells and helps with skin growth and maintenance.[6]

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.

Interactions

Cystatin A has been shown to interact with Cathepsin B[7][8] and CTSL1.[8][9]

Clinical significance

Altered levels of cystatin A have been observed in several disease states, particularly in skin disorders and certain cancers.[10] Its role as a protease inhibitor makes it potentially valuable as both a diagnostic marker and therapeutic target.[11]

See also

References

Page Template:Reflist/styles.css has no content.

  1. ^ Page Module:Citation/CS1/styles.css has no content.Hsieh WT, Barrick JL, Berrettini WH, Chan MM, Fong D (April 1991). "A PstI DNA polymorphism in the human stefin A gene (STF 1)". Nucleic Acids Research. 19 (7): 1722. doi:10.1093/nar/19.7.1722-a. PMC 333958. PMID 1674139.
  2. ^ a b Page Module:Citation/CS1/styles.css has no content."Entrez Gene: CSTA cystatin A (stefin A)".
  3. ^ a b c d Page Module:Citation/CS1/styles.css has no content.Shimba N, Kariya E, Tate S, Kaji H, Kainosho M (2000). "Structural comparison between wild-type and P25S human cystatin A by NMR spectroscopy. Does this mutation affect the alpha-helix conformation?". Journal of Structural and Functional Genomics. 1 (1): 26–42. doi:10.1023/A:1011380315619. PMID 12836678.
  4. ^ Page Module:Citation/CS1/styles.css has no content.Pavlova A, Björk I (November 2002). "The role of the second binding loop of the cysteine protease inhibitor, cystatin A (stefin A), in stabilizing complexes with target proteases is exerted predominantly by Leu73". European Journal of Biochemistry. 269 (22): 5649–5658. doi:10.1046/j.1432-1033.2002.03273.x. PMID 12423365.
  5. ^ a b Page Module:Citation/CS1/styles.css has no content.Estrada S, Pavlova A, Björk I (June 1999). "The contribution of N-terminal region residues of cystatin A (stefin A) to the affinity and kinetics of inhibition of papain, cathepsin B, and cathepsin L". Biochemistry. 38 (22): 7339–7345. doi:10.1021/bi990003s. PMID 10353845.
  6. ^ Page Module:Citation/CS1/styles.css has no content.Hsieh WT, Barrick JL, Berrettini WH, Chan MM, Fong D (April 1991). "A PstI DNA polymorphism in the human stefin A gene (STF 1)". Nucleic Acids Research. 19 (7): 1722. doi:10.1093/nar/19.7.1722-a. PMC 333958. PMID 1674139.
  7. ^ Page Module:Citation/CS1/styles.css has no content.Pavlova A, Björk I (September 2003). "Grafting of features of cystatins C or B into the N-terminal region or second binding loop of cystatin A (stefin A) substantially enhances inhibition of cysteine proteinases". Biochemistry. 42 (38): 11326–11333. doi:10.1021/bi030119v. PMID 14503883.
  8. ^ a b Page Module:Citation/CS1/styles.css has no content.Estrada S, Nycander M, Hill NJ, Craven CJ, Waltho JP, Björk I (May 1998). "The role of Gly-4 of human cystatin A (stefin A) in the binding of target proteinases. Characterization by kinetic and equilibrium methods of the interactions of cystatin A Gly-4 mutants with papain, cathepsin B, and cathepsin L". Biochemistry. 37 (20): 7551–7560. doi:10.1021/bi980026r. PMID 9585570.
  9. ^ Page Module:Citation/CS1/styles.css has no content.Majerle A, Jerala R (September 2003). "Protein inhibitors form complexes with procathepsin L and augment cleavage of the propeptide". Archives of Biochemistry and Biophysics. 417 (1): 53–58. doi:10.1016/S0003-9861(03)00319-9. PMID 12921779.
  10. ^ Page Module:Citation/CS1/styles.css has no content.Rinne A (April 2010). "Epidermal SH-protease inhibitor (ACPI, cystatin A) in cancer. A short historical review". Pathology, Research and Practice. 206 (4): 259–262. doi:10.1016/j.prp.2009.12.005. PMID 20116931.
  11. ^ Page Module:Citation/CS1/styles.css has no content.Xie Q, Liu L, Chen X, Cheng Y, Li J, Zhang X, et al. (2021-06-22). "Identification of Cysteine Protease Inhibitor CST2 as a Potential Biomarker for Colorectal Cancer". Journal of Cancer. 12 (17): 5144–5152. doi:10.7150/jca.53983. PMC 8317524. PMID 34335931.{{cite journal}}: CS1 maint: overridden setting (link)

Further reading

Page Template:Refbegin/styles.css has no content.

Lua error in package.lua at line 80: module 'Module:Navbox/configuration' not found.

Retrieved from "https://cosmopedia.co/index.php?title=Cystatin_A&oldid=4923123"