Coding

Part:BBa_K4165085

Designed by: Mennatallah Mahmoud Mohamed Abdelzaher Turky   Group: iGEM22_CU_Egypt   (2022-09-30)
Revision as of 12:36, 13 October 2022 by Omnia Alaa11 (Talk | contribs)

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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


Assembly Compatibility:
  • 10
    COMPATIBLE WITH RFC[10]
  • 12
    COMPATIBLE WITH RFC[12]
  • 21
    COMPATIBLE WITH RFC[21]
  • 23
    COMPATIBLE WITH RFC[23]
  • 25
    COMPATIBLE WITH RFC[25]
  • 1000
    COMPATIBLE WITH RFC[1000]


Dry-Lab Characterization

Modelling

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

Quality Assessment

cbeta_deviations clashscore molprobity ramachandran_favored ramachandran_outliers Qmean_4 Qmean_6
0 50.77 3.2 78.95 8.42 -3.71517 -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.


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