Coding

Part:BBa_K4165076

Designed by: Mennatallah Mahmoud Mohamed Abdelzaher Turky   Group: iGEM22_CU_Egypt   (2022-09-30)
Revision as of 13:01, 6 October 2022 by Ahmedsameh (Talk | contribs)


SPINK1 (Serine Peptidase Inhibitor Kazal type 1).

This basic part encodes Human serine protease inhibitor known as SPINK1 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 able to inhibit trypsins. The inhibitor is secreted from pancreatic acinar cells into the pancreatic juice. The main function of the inhibitor in pancreatic juice is the prevention of activation of immature trypsin zymogens within the pancreatic duct. The inhibitor binds to trypsin 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]


Parameters

GC% Content 56.5%

Isoelectric point (PI) 7.338

Charge at pH 7 0.508

Molecular Weight (Protein) 8.507 kDa

It has both x-ray structure and a predicted model (AlphaFold2). PDB structure

Structure assessment

X-ray structure: https://drive.google.com/drive/folders/1o_e_vCFs-bwbqS0z-3XsDzY9ENKnag4I Molprobity: 2.47 Clash Score: 9.35 Ramachandran Favoured: 94.44% Ramachandran Outliers: 0% Rotamers Outliers: 6% C-beta Deviations: 0% Q-Mean: 0.83 土 0.11 


                 Figure 1.: A graphical illustration showing the structure of SPINK1 (X-ray).



AlphaFold: https://drive.google.com/drive/folders/1o_e_vCFs-bwbqS0z-3XsDzY9ENKnag4I Molprobity: 1.11 Clash Score: 0 Ramachandran Favoured: 92.21% Ramachandran Outliers: 0% Rotamers Outliers: 1.49% C-beta Deviations: 0% Q-Mean: 0.65 土 0.1 



                 Figure 2.: A graphical illustration showing the structure of SPINK1 (AlphaFold).


References

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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