Difference between revisions of "Part:BBa K4165085"

Revision as of 05:32, 12 October 2022

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

Dry-Lab Characterization

Modelling

This inhibitor was modeled by several software and the top model was acquired by Alphafold

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

                 Figure 1.: A graphical illustration showing the structure of the inhibitor (Model 4-AlphaFold).

Docking

ΔG = -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.