Part:BBa_K4165077
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
- 10INCOMPATIBLE WITH RFC[10]Illegal PstI site found at 49
Illegal PstI site found at 198 - 12INCOMPATIBLE WITH RFC[12]Illegal PstI site found at 49
Illegal PstI site found at 198 - 21COMPATIBLE WITH RFC[21]
- 23INCOMPATIBLE WITH RFC[23]Illegal PstI site found at 49
Illegal PstI site found at 198 - 25INCOMPATIBLE WITH RFC[25]Illegal PstI site found at 49
Illegal PstI site found at 198 - 1000COMPATIBLE WITH RFC[1000]
Dry Lab Characterization
This inhibitor was modeled by several software and the top model was acquired by Alphafold2
Functional Parameters
Isoelectric point (PI): 8.121 Charge at pH 7: 4.499 Molecular Weight (Protein): 8.943
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.
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