3DFJ
Crystal structure of human Prostasin
Summary for 3DFJ
| Entry DOI | 10.2210/pdb3dfj/pdb |
| Related | 3DFL |
| Descriptor | Prostasin, CHLORIDE ION (3 entities in total) |
| Functional Keywords | prostasin, serine protease, glycoprotein, hydrolase, membrane, secreted, transmembrane, zymogen |
| Biological source | Homo sapiens |
| Cellular location | Prostasin: Cell membrane; Single-pass membrane protein. Prostasin light chain: Secreted, extracellular space. Prostasin heavy chain: Secreted, extracellular space: Q16651 |
| Total number of polymer chains | 1 |
| Total formula weight | 28459.65 |
| Authors | Su, H.P.,Rickert, K.W.,Darke, P.L.,Munshi, S.K. (deposition date: 2008-06-12, release date: 2008-10-14, Last modification date: 2024-10-09) |
| Primary citation | Rickert, K.W.,Kelley, P.,Byrne, N.J.,Diehl, R.E.,Hall, D.L.,Montalvo, A.M.,Reid, J.C.,Shipman, J.M.,Thomas, B.W.,Munshi, S.K.,Darke, P.L.,Su, H.P. Structure of human prostasin, a target for the regulation of hypertension. J.Biol.Chem., 283:34864-34872, 2008 Cited by PubMed Abstract: Prostasin (also called channel activating protease-1 (CAP1)) is an extracellular serine protease implicated in the modulation of fluid and electrolyte regulation via proteolysis of the epithelial sodium channel. Several disease states, particularly hypertension, can be affected by modulation of epithelial sodium channel activity. Thus, understanding the biochemical function of prostasin and developing specific agents to inhibit its activity could have a significant impact on a widespread disease. We report the expression of the prostasin proenzyme in Escherichia coli as insoluble inclusion bodies, refolding and activating via proteolytic removal of the N-terminal propeptide. The refolded and activated enzyme was shown to be pure and monomeric, with kinetic characteristics very similar to prostasin expressed from eukaryotic systems. Active prostasin was crystallized, and the structure was determined to 1.45 A resolution. These apoprotein crystals were soaked with nafamostat, allowing the structure of the inhibited acyl-enzyme intermediate structure to be determined to 2.0 A resolution. Comparison of the inhibited and apoprotein forms of prostasin suggest a mechanism of regulation through stabilization of a loop which interferes with substrate recognition. PubMed: 18922802DOI: 10.1074/jbc.M805262200 PDB entries with the same primary citation |
| Experimental method | X-RAY DIFFRACTION (1.45 Å) |
Structure validation
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