Part:BBa_K4165078

SPINK6 (Serine Peptidase Inhibitor Kazal type 6).

This basic part encodes Human serine protease inhibitor known as SPINK6 which is able to inhibit serine peptidases.

Usage and Biology

This type of family encodes for a type of inhibitor that is able to inhibit serine peptidases, especially kallkreins. The inhibitor’s main function is to inhibit kallikrein-related peptidases in the skin. The inhibitor binds to serine peptidases and since the catalytic core of HtrA1 (BBa_K4165004) is considered as a serine 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
  INCOMPATIBLE WITH RFC[21]

  Illegal BamHI site found at 102
  
• 23
  COMPATIBLE WITH RFC[23]
• 25
  COMPATIBLE WITH RFC[25]
• 1000
  COMPATIBLE WITH RFC[1000]

Functional Parameters

GC% Content 54.6% Isoelectric point (PI) 8.117 Charge at pH 7 3.635 Molecular Weight (Protein) 8.585 kDa

It has both NMR structure and a predicted model (AlphaFold2).

PDB structure: https://drive.google.com/drive/folders/1OhqZoqIootmRPpiVkemM_npNaA5WMO9b

NMR structure: https://www.rcsb.org/structure/2N52 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 the inhibitor (NMR).

AlphaFold2: 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 the inhibitor (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.