Part:BBa_K4165090

WAP-four disulfide core domain 6 serine protease inhibitor.

This basic part encodes Human serine protease inhibitor WAP-four disulfide core domain 6 which is able to inhibit HtrA1 (BBa_K4165004).

Usage and Biology

This type of family encodes for a type of inhibitor that contains a motif which has 8 cysteine residues capable of forming four disulfide bonds at the core of the protease, thus inhibiting its action. This type of inhibitor is very effective and has high affinity for trypsin-like proteases (serine proteases), and in our case it would act as an inhibitor for the trypsin-like catalytic domain of serine protease 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
  INCOMPATIBLE WITH RFC[25]

  Illegal NgoMIV site found at 252
  
• 1000
  COMPATIBLE WITH RFC[1000]

Functional Parameters

GC Content% 63.6%

Isoelectric point (PI) 7.981

Charge at pH 7 4.57

Molecular Weight (Protein) 14.626 kDa

PDB Structures

The predicted structure (AlphaFold2) is presented.

AlphaFold2 https://alphafold.ebi.ac.uk/entry/Q9BQY6 Q_Mean = Ramachandran Favoured = Ramachandran Outliers = Clash Score = C-beta Deviation = Rotamers outliers = Total Score =

References

1. Clauss, A., Lilja, H., & Lundwall, Å. (2005). The evolution of a genetic locus encoding small serine proteinase inhibitors. Biochemical and biophysical research communications, 333(2), 383-389. 2. 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. 3. 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.