Difference between revisions of "Part:BBa K4165077"

Revision as of 18:07, 10 October 2022

WAP-four disulphide core domain 10A serine protease inhibitor.

This basic part encodes Human serine protease inhibitor WAP-four disulfide core domain 10A which is able to inhibit HtrA1 (BBa_K4165004).

Usage and Biology

This gene encodes for a type of inhibitor that contains a motif which consists of 8 cysteine residues capable of forming four disulfide bonds at the core of the protease, thus inhibiting its action. This type of inhibitor is very effective and has high affinity for trypsin-like proteases (serine proteases), and in our case it would act as an inhibitor for the trypsin-like catalytic domain of serine protease HtrA1[1]-[3].

Sequence and Features

Functional Parameters

Isoelectric point (PI) 8.121 Charge at pH 7 4.499 Molecular Weight (Protein) 8.943

Homology and denovo modelling - AlphaFold2 PDB structure https://drive.google.com/drive/folders/1Xzf25fsOO8fyS0w3xAookPZnMpGQ6vrQ
Structure assessment results:
Molprobity = 1.62
Q_Mean = 0.6 土 0.1
Ramachandran Favoured = 89.61%
Ramachandran Outliers = 0
Clash Score = 0
C-beta Deviation = 0
Total Score = 5

                 Figure 1.: A graphical illustration showing the structure of the inhibitor (AlphaFold).

References

1. Clauss, A., Lilja, H., & Lundwall, Å. (2005). The evolution of a genetic locus encoding small serine proteinase inhibitors. Biochemical and biophysical research communications, 333(2), 383-389. 2. Eigenbrot, C., Ultsch, M., Lipari, M. T., Moran, P., Lin, S. J., Ganesan, R., ... & Kirchhofer, D. (2012). Structural and functional analysis of HtrA1 and its subdomains. Structure, 20(6), 1040-1050. 3. Grau, S., Baldi, A., Bussani, R., Tian, X., Stefanescu, R., Przybylski, M., ... & Ehrmann, M. (2005). Implications of the serine protease HtrA1 in amyloid precursor protein processing. Proceedings of the National Academy of Sciences, 102(17), 6021-6026.