Part:BBa_K4165091
SLPI (Secretory leukocyte peptidase inhibitor).
This basic part encodes Human serine protease inhibitor secretory leukocyte peptidase inhibitor which is predicted to be able to inhibit HtrA1 (BBa_K4165004).
Usage and Biology
This type of inhibitor is considered to be an acid stable inhibitor with very high affinity for trypsins, chymotrypsine, elastases, and cathepsin G [1-6]. 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[7-9].
Sequence and Features
- 10COMPATIBLE WITH RFC[10]
- 12COMPATIBLE WITH RFC[12]
- 21INCOMPATIBLE WITH RFC[21]Illegal BamHI site found at 219
- 23COMPATIBLE WITH RFC[23]
- 25COMPATIBLE WITH RFC[25]
- 1000COMPATIBLE WITH RFC[1000]
Functional Parameters
GC Content% 67.2% Isoelectric point (PI) 8.494 Charge at pH 7 10.831 Molecular Weight (Protein) 14.326
PDB structure
X-ray and denovo modelling - AlphaFold2
X-ray: https://www.rcsb.org/structure/2Z7F Molprobity = Q_Mean = Ramachandran Favoured = Ramachandran Outliers = Clash Score = C-beta Deviation = Rotamers outliers = Total Score =
AlphaFold: https://alphafold.ebi.ac.uk/entry/P03973 Molprobity = Q_Mean = Ramachandran Favoured = Ramachandran Outliers = Clash Score = C-beta Deviation = Rotamers outliers = Total Score =
Figure 1.: A graphical illustration showing the structure of the inhibitor.
References
1- HEINZEL, R., APPELHANS, H., GASSEN, G., SEEMÜLLER, U., MACHLEIDT, W., FRITZ, H., & STEFFENS, G. (1986). Molecular cloning and expression of cDNA for human antileukoprotease from cervix uterus. European journal of biochemistry, 160(1), 61-67.
2- Thompson, R. C., & Ohlsson, K. (1986). Isolation, properties, and complete amino acid sequence of human secretory leukocyte protease inhibitor, a potent inhibitor of leukocyte elastase. Proceedings of the National Academy of Sciences, 83(18), 6692-6696.
3- Thompson, R. C., & Ohlsson, K. (1986). Isolation, properties, and complete amino acid sequence of human secretory leukocyte protease inhibitor, a potent inhibitor of leukocyte elastase. Proceedings of the National Academy of Sciences, 83(18), 6692-6696.
4- Eisenberg, S. P., Hale, K. K., Heimdal, P., & Thompson, R. C. (1990). Location of the protease-inhibitory region of secretory leukocyte protease inhibitor. Journal of Biological Chemistry, 265(14), 7976-7981.
5- Mulligan, M. S., Lentsch, A. B., Huber-Lang, M., Guo, R. F., Sarma, V., Wright, C. D., ... & Ward, P. A. (2000). Anti-inflammatory effects of mutant forms of secretory leukocyte protease inhibitor. The American journal of pathology, 156(3), 1033-1039.
6- Fukushima, K., Kamimura, T., & Takimoto-Kamimura, M. (2013). Structure basis 1/2SLPI and porcine pancreas trypsin interaction. Journal of synchrotron radiation, 20(6), 943-947.
7- 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.
8- 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.
9- 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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