1K9O

CRYSTAL STRUCTURE OF MICHAELIS SERPIN-TRYPSIN COMPLEX

Replaces:  1I99

Summary for 1K9O

• Entry DOI: 10.2210/pdb1k9o/pdb
• Descriptor: ALASERPIN, TRYPSIN II ANIONIC (3 entities in total)
• Functional Keywords: michaelis serpin-protease complex inhibitory triad, hydrolase-hydrolase inhibitor complex, hydrolase/hydrolase inhibitor
• Biological source: Manduca sexta (tobacco hornworm); More
• Cellular location: Secreted, extracellular space: P14754 P00763
• Total number of polymer chains: 2
• Total formula weight: 65815.83

Authors

Ye, S.,Cech, A.L.,Belmares, R.,Bergstrom, R.C.,Tong, Y.,Corey, D.R.,Kanost, M.R.,Goldsmith, E.J. (deposition date: 2001-10-29, release date: 2001-11-21, Last modification date: 2024-10-30)

Primary citation

Ye, S.,Cech, A.L.,Belmares, R.,Bergstrom, R.C.,Tong, Y.,Corey, D.R.,Kanost, M.R.,Goldsmith, E.J.
The structure of a Michaelis serpin-protease complex.
Nat.Struct.Biol., 8:979-983, 2001

PubMed Abstract: Serine protease inhibitors (serpins) regulate the activities of circulating proteases. Serpins inhibit proteases by acylating the serine hydroxyl at their active sites. Before deacylation and complete proteolysis of the serpin can occur, massive conformational changes are triggered in the serpin while maintaining the covalent linkage between the protease and serpin. Here we report the structure of a serpin-trypsin Michaelis complex, which we visualized by using the S195A trypsin mutant to prevent covalent complex formation. This encounter complex reveals a more extensive interaction surface than that present in small inhibitor-protease complexes and is a template for modeling other serpin-protease pairs. Mutations of several serpin residues at the interface reduced the inhibitory activity of the serpin. The serine residue C-terminal to the scissile peptide bond is found in a closer than usual interaction with His 57 at the active site of trypsin.

PubMed: 11685246
DOI: 10.1038/nsb1101-979

Experimental method

X-RAY DIFFRACTION (2.3 Å)