Part:BBa_K4165085
SPINK14 (Serine Peptidase Inhibitor Kazal type 14).
This basic part encodes Human serine protease inhibitor known as SPINK14 which is able to inhibit trypsin-like proteases, like HtrA1 (BBa_K4165004).
Usage and Biology
This type of family encodes for a type of inhibitor that is predicted to be able to inhibit serine peptidases. The inhibitor is present extracellularly. The inhibitor binds to trypsin-like proteases (serine proteases) and since the catalytic core of HtrA1 (BBa_K4165004) is considered as a trypsin-like catalytic domain, so this inhibitor also is considered to inhibit the function of HtrA1 [1-3].
Sequence and Features
- 10COMPATIBLE WITH RFC[10]
- 12COMPATIBLE WITH RFC[12]
- 21COMPATIBLE WITH RFC[21]
- 23COMPATIBLE WITH RFC[23]
- 25COMPATIBLE WITH RFC[25]
- 1000COMPATIBLE WITH RFC[1000]
Dry-Lab Characterization
Quality Assessment
C-beta deviation: 0
Clash score: 50.77
Molprobity: 3.2
Ramachandran favored: 78.95
Ramachandran outliers: 8.42
QMean_4: -3.71517
QMean_6: -3.3123
Modelling
Figure 1.: A graphical illustration showing the structure of the inhibitor (Model 4-AlphaFold).
Docking
Gibbs Free Energy is -37.794
Figure 2.: A graphical illustration showing the binding of the inhibitor with HtrA1 (Galaxy).
Reference:
1 - Frochaux, V., Hildebrand, D., Talke, A., Linscheid, M. W., & Schlüter, H. (2014). Alpha-1-antitrypsin: a novel human high temperature requirement protease A1 (HTRA1) substrate in human placental tissue. PloS one, 9(10), e109483.
2 - 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.
3 - 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.
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