1F34

CRYSTAL STRUCTURE OF ASCARIS PEPSIN INHIBITOR-3 BOUND TO PORCINE PEPSIN

Summary for 1F34

• Entry DOI: 10.2210/pdb1f34/pdb
• Related: 1F32
• Descriptor: PEPSIN A, MAJOR PEPSIN INHIBITOR PI-3, (4S)-2-METHYL-2,4-PENTANEDIOL, ... (4 entities in total)
• Functional Keywords: proteinase-inhibitor complex, hydrolase-hydrolase inhibitor complex, hydrolase/hydrolase inhibitor
• Biological source: Ascaris suum (pig roundworm); More
• Cellular location: Secreted: P00791 P19400
• Total number of polymer chains: 2
• Total formula weight: 51123.35

Authors

Ng, K.K.,Petersen, J.F.,Cherney, M.M.,Garen, C.,James, M.N. (deposition date: 2000-05-31, release date: 2001-02-01, Last modification date: 2024-11-13)

Primary citation

Ng, K.K.,Petersen, J.F.,Cherney, M.M.,Garen, C.,Zalatoris, J.J.,Rao-Naik, C.,Dunn, B.M.,Martzen, M.R.,Peanasky, R.J.,James, M.N.
Structural basis for the inhibition of porcine pepsin by Ascaris pepsin inhibitor-3.
Nat.Struct.Biol., 7:653-657, 2000

PubMed Abstract: The three-dimensional structures of pepsin inhibitor-3 (PI-3) from Ascaris suum and of the complex between PI-3 and porcine pepsin at 1. 75 A and 2.45 A resolution, respectively, have revealed the mechanism of aspartic protease inhibition by this unique inhibitor. PI-3 has a new fold consisting of two domains, each comprising an antiparallel beta-sheet flanked by an alpha-helix. In the enzyme-inhibitor complex, the N-terminal beta-strand of PI-3 pairs with one strand of the 'active site flap' (residues 70-82) of pepsin, thus forming an eight-stranded beta-sheet that spans the two proteins. PI-3 has a novel mode of inhibition, using its N-terminal residues to occupy and therefore block the first three binding pockets in pepsin for substrate residues C-terminal to the scissile bond (S1'-S3'). The molecular structure of the pepsin-PI-3 complex suggests new avenues for the rational design of proteinaceous aspartic proteinase inhibitors.

PubMed: 10932249
DOI: 10.1038/77950

Experimental method

X-RAY DIFFRACTION (2.45 Å)