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
- 10INCOMPATIBLE WITH RFC[10]Illegal PstI site found at 40
- 12INCOMPATIBLE WITH RFC[12]Illegal PstI site found at 40
- 21COMPATIBLE WITH RFC[21]
- 23INCOMPATIBLE WITH RFC[23]Illegal PstI site found at 40
- 25INCOMPATIBLE WITH RFC[25]Illegal PstI site found at 40
- 1000COMPATIBLE WITH RFC[1000]
Functional Parameters
| GC Content% | Isoelectric point (PI) | Charge at pH 7 | Molecular Weight (Protein) |
|---|---|---|---|
| 66.8 | 7.225 | 0.376 | 21.057 kDa |
Modeling
The available structures are the predicted one (AlphaFold) and the x-ray structures.
Figure 1.: A graphical illustration showing the structure of the inhibitor (X-Ray diffraction).
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.
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