1PSO

The crystal structure of human pepsin and its complex with pepstatin

Summary for 1PSO

• Entry DOI: 10.2210/pdb1pso/pdb
• Related PRD ID: PRD_000557
• Descriptor: PEPSIN 3A, PEPSTATIN (3 entities in total)
• Functional Keywords: acid proteinase, hydrolase-hydrolase inhibitor complex, hydrolase/hydrolase inhibitor
• Biological source: Homo sapiens (human); More
• Cellular location: Secreted: P00790
• Total number of polymer chains: 2
• Total formula weight: 35317.78

Authors

Fujinaga, M.,Chernaia, M.M.,Tarasova, N.,Mosimann, S.C.,James, M.N.G. (deposition date: 1995-01-23, release date: 1995-04-20, Last modification date: 2024-10-09)

Primary citation

Fujinaga, M.,Chernaia, M.M.,Tarasova, N.I.,Mosimann, S.C.,James, M.N.
Crystal structure of human pepsin and its complex with pepstatin.
Protein Sci., 4:960-972, 1995

PubMed Abstract: The three-dimensional crystal structure of human pepsin and that of its complex with pepstatin have been solved by X-ray crystallographic methods. The native pepsin structure has been refined with data collected to 2.2 A resolution to an R-factor of 19.7%. The pepsin:pepstatin structure has been refined with data to 2.0 A resolution to an R-factor of 18.5%. The hydrogen bonding interactions and the conformation adopted by pepstatin are very similar to those found in complexes of pepstatin with other aspartic proteinases. The enzyme undergoes a conformational change upon inhibitor binding to enclose the inhibitor more tightly. The analysis of the binding sites indicates that they form an extended tube without distinct binding pockets. By comparing the residues on the binding surface with those of the other human aspartic proteinases, it has been possible to rationalize some of the experimental data concerning the different specificities. At the S1 site, valine at position 120 in renin instead of isoleucine, as in the other enzymes, allows for binding of larger hydrophobic residues. The possibility of multiple conformations for the P2 residue makes the analysis of the S2 site difficult. However, it is possible to see that the specific interactions that renin makes with histidine at P2 would not be possible in the case of the other enzymes. At the S3 site, the smaller volume that is accessible in pepsin compared to the other enzymes is consistent with its preference for smaller residues at the P3 position.

PubMed: 7663352

Experimental method

X-RAY DIFFRACTION (2 Å)