3e16

X-ray structure of human prostasin in complex with Benzoxazole warhead peptidomimic, lysine in P3X-ray structure of human prostasin in complex with Benzoxazole warhead peptidomimic, lysine in P3

Structural highlights

3e16 is a 1 chain structure with sequence from Human. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Ligands:	, ,
Related:	3eon, 3eop, 3e1x
Gene:	PRSS8 (HUMAN)
Resources:	FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Function

[PRSS8_HUMAN] Possesses a trypsin-like cleavage specificity with a preference for poly-basic substrates. Stimulates epithelial sodium channel (ENaC) activity through activating cleavage of the gamma subunits (SCNN1G).^[1] ^[2]

Evolutionary Conservation

Check, as determined by ConSurfDB. You may read the explanation of the method and the full data available from ConSurf.

Publication Abstract from PubMed

Structure-based design was utilized to guide the early stage optimization of a substrate-like inhibitor to afford potent peptidomimetic inhibitors of the channel-activating protease prostasin. The first X-ray crystal structures of prostasin with small molecule inhibitors bound to the active site are also reported.

Discovery of inhibitors of the channel-activating protease prostasin (CAP1/PRSS8) utilizing structure-based design.,Tully DC, Vidal A, Chatterjee AK, Williams JA, Roberts MJ, Petrassi HM, Spraggon G, Bursulaya B, Pacoma R, Shipway A, Schumacher AM, Danahay H, Harris JL Bioorg Med Chem Lett. 2008 Nov 15;18(22):5895-9. Epub 2008 Aug 14. PMID:18752942^[3]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

References

↑ Tong Z, Illek B, Bhagwandin VJ, Verghese GM, Caughey GH. Prostasin, a membrane-anchored serine peptidase, regulates sodium currents in JME/CF15 cells, a cystic fibrosis airway epithelial cell line. Am J Physiol Lung Cell Mol Physiol. 2004 Nov;287(5):L928-35. Epub 2004 Jul 9. PMID:15246975 doi:http://dx.doi.org/10.1152/ajplung.00160.2004
↑ Shipway A, Danahay H, Williams JA, Tully DC, Backes BJ, Harris JL. Biochemical characterization of prostasin, a channel activating protease. Biochem Biophys Res Commun. 2004 Nov 12;324(2):953-63. PMID:15474520 doi:http://dx.doi.org/10.1016/j.bbrc.2004.09.123
↑ Tully DC, Vidal A, Chatterjee AK, Williams JA, Roberts MJ, Petrassi HM, Spraggon G, Bursulaya B, Pacoma R, Shipway A, Schumacher AM, Danahay H, Harris JL. Discovery of inhibitors of the channel-activating protease prostasin (CAP1/PRSS8) utilizing structure-based design. Bioorg Med Chem Lett. 2008 Nov 15;18(22):5895-9. Epub 2008 Aug 14. PMID:18752942 doi:10.1016/j.bmcl.2008.08.029

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OCA

[1] Tong Z, Illek B, Bhagwandin VJ, Verghese GM, Caughey GH. Prostasin, a membrane-anchored serine peptidase, regulates sodium currents in JME/CF15 cells, a cystic fibrosis airway epithelial cell line. Am J Physiol Lung Cell Mol Physiol. 2004 Nov;287(5):L928-35. Epub 2004 Jul 9. PMID:15246975 doi:http://dx.doi.org/10.1152/ajplung.00160.2004

[2] Shipway A, Danahay H, Williams JA, Tully DC, Backes BJ, Harris JL. Biochemical characterization of prostasin, a channel activating protease. Biochem Biophys Res Commun. 2004 Nov 12;324(2):953-63. PMID:15474520 doi:http://dx.doi.org/10.1016/j.bbrc.2004.09.123

[3] Tully DC, Vidal A, Chatterjee AK, Williams JA, Roberts MJ, Petrassi HM, Spraggon G, Bursulaya B, Pacoma R, Shipway A, Schumacher AM, Danahay H, Harris JL. Discovery of inhibitors of the channel-activating protease prostasin (CAP1/PRSS8) utilizing structure-based design. Bioorg Med Chem Lett. 2008 Nov 15;18(22):5895-9. Epub 2008 Aug 14. PMID:18752942 doi:10.1016/j.bmcl.2008.08.029

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