2CV3

Crystal structure of porcine pancreatic elastase complexed with a macroclyclic peptide inhibitor

Summary for 2CV3

• Entry DOI: 10.2210/pdb2cv3/pdb
• Related PRD ID: PRD_000571
• Descriptor: Elastase 1, Inhibitor FR901451 (3 entities in total)
• Functional Keywords: protein-inhibitor interaction, macrocyclic peptide, hydrolase-hydrolase inhibitor complex, hydrolase/hydrolase inhibitor
• Biological source: Sus scrofa (pig); More
• Cellular location: Secreted: P00772
• Total number of polymer chains: 2
• Total formula weight: 27254.42

Authors

Kinoshita, T.,Tada, T.,Kitatani, T. (deposition date: 2005-05-31, release date: 2006-05-16, Last modification date: 2024-10-23)

Primary citation

Kinoshita, T.,Kitatani, T.,Warizaya, M.,Tada, T.
Structure of the complex of porcine pancreatic elastase with a trimacrocyclic peptide inhibitor FR901451
Acta Crystallogr.,Sect.F, 61:808-811, 2005

PubMed Abstract: Porcine pancreatic elastase (PPE) resembles the attractive drug target leukocyte elastase, which has the ability to degrade connective tissue in the body. The crystal structure of PPE complexed with a novel trimacrocyclic peptide inhibitor, FR901451, was solved at 1.9 A resolution. The inhibitor occupied the subsites S3 through S3' of PPE and induced conformational changes in the side chains of Arg64 and Arg226, which are located at the edges of the substrate-binding cleft. Structural comparison of five PPE-inhibitor complexes, including the FR901451 complex and non-ligated PPE, reveals that the residues forming the S2, S1, S1' and S2' subsites in the cleft are rigid, but the two arginine residues playing a part in the S3 and S3' subsites are flexible. Structural comparison of PPE with human leukocyte elastase (HLE) implies that the inhibitor binds to HLE in a similar manner to the FR901451-PPE complex. This structural insight may help in the design of potent elastase inhibitors.

PubMed: 16511165
DOI: 10.1107/S1744309105026047

Experimental method

X-RAY DIFFRACTION (1.9 Å)