Part:BBa_K4165094

Phosphatidylethanolamine-binding protein 1(PEBP1).

This basic part encodes Human serine protease inhibitor phosphotidylethanolamine-binding protein 1 which is able to inhibit HtrA1 (BBa_K4165004).

Usage and Biology

ATP, opioids, and phosphatidylethanolamine are all bound. Phosphatidylinositol and phosphatidylcholine have a lesser affinity for it. Inhibits thrombin, neuropsin, and chymotrypsin but not trypsin, tissue type plasminogen activator, and elastase (By similarity). RAF1 kinase activity is inhibited by preventing its activation, dissociating the RAF1/MEK complex, and serving as a competitive inhibitor of MEK phosphorylation. HCNP may be implicated in the function of central nervous system presynaptic cholinergic neurons. HCNP enhances choline acetyltransferase synthesis but not acetylcholinesterase.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
  INCOMPATIBLE WITH RFC[10]

  Illegal PstI site found at 40
  
• 12
  INCOMPATIBLE WITH RFC[12]

  Illegal PstI site found at 40
  
• 21
  COMPATIBLE WITH RFC[21]
• 23
  INCOMPATIBLE WITH RFC[23]

  Illegal PstI site found at 40
  
• 25
  INCOMPATIBLE WITH RFC[25]

  Illegal PstI site found at 40
  
• 1000
  COMPATIBLE WITH RFC[1000]

Functional Parameters

GC Content% 66.8%

Isoelectric point (PI) 7.225

Charge at pH 7 0.376

Molecular Weight (Protein) 21.057 kDa

PDB Sturcture

The available structures are the predicted one (AlphaFold) and the x-ray structures.

X-ray https://www.rcsb.org/structure/1BD9

                 Figure 1.: A graphical illustration showing the structure of the inhibitor (X-Ray diffraction).

AlphaFold https://alphafold.ebi.ac.uk/entry/P30086

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

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.