Part:BBa_K4165089
WAP-four disulfide core domain 2 serine protease inhibitor.
This basic part encodes Human serine protease inhibitor WAP-four disulfide core domain 2 which is able to inhibit HtrA1 (BBa_K4165004).
Usage and Biology
This type of family 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. The main function of this inhibitor is to pervent elastase-mediated tissue proteolysis. 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 115
Illegal PstI site found at 183 - 12INCOMPATIBLE WITH RFC[12]Illegal PstI site found at 115
Illegal PstI site found at 183 - 21COMPATIBLE WITH RFC[21]
- 23INCOMPATIBLE WITH RFC[23]Illegal PstI site found at 115
Illegal PstI site found at 183 - 25INCOMPATIBLE WITH RFC[25]Illegal PstI site found at 115
Illegal PstI site found at 183
Illegal NgoMIV site found at 3 - 1000COMPATIBLE WITH RFC[1000]
Functional Parameters
GC Content% 68.8%
Isoelectric point (PI) 4.371
Charge at pH 7 -4.23
Molecular Weight (Protein) 12.993 kDa
PDB structure
The predicted structure (AlphaFold2) is presented.
AlphaFold2 https://alphafold.ebi.ac.uk/entry/Q14508 Q_Mean = Ramachandran Favoured = Ramachandran Outliers = Clash Score = C-beta Deviation = Rotamers outliers = Total Score =
Figure 1.: A graphical illustration showing the structure of the inhibitor.
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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