Part:BBa_K4165088

WAP-four disulfide core domain 14 serine protease inhibitor.

This basic part encodes Human serine protease inhibitor WAP-four disulfide core domain 14 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 consists of 8 cysteine residues capable of forming four disulfide bonds at the core of the protease, thus inhibiting its action. The main function of this inhibitor is to prevent elastase-mediated tissue proteolysis. 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
  INCOMPATIBLE WITH RFC[21]

  Illegal BamHI site found at 132
  
• 23
  COMPATIBLE WITH RFC[23]
• 25
  INCOMPATIBLE WITH RFC[25]

  Illegal AgeI site found at 189
  
• 1000
  COMPATIBLE WITH RFC[1000]

Functional Parameters

GC Content% 67.5%

Isoelectric point (PI) 8.641

Charge at pH 7 6.373

Molecular Weight (Protein) 12.27 kDa

PDB structure

X-ray, NMR, and the predicted structures (AlphaFold2) are all present.

X-ray https://www.rcsb.org/structure/1FLE Q_Mean = Ramachandran Favoured = Ramachandran Outliers = Clash Score = C-beta Deviation = Rotamers outliers = Total Score =

NMR: https://www.rcsb.org/structure/2REL Q_Mean = Ramachandran Favoured = Ramachandran Outliers = Clash Score = C-beta Deviation = Rotamers outliers = Total Score =

AlphaFold https://alphafold.ebi.ac.uk/entry/P19957 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.