1AYE

HUMAN PROCARBOXYPEPTIDASE A2

Summary for 1AYE

• Entry DOI: 10.2210/pdb1aye/pdb
• Descriptor: PROCARBOXYPEPTIDASE A2, ZINC ION (3 entities in total)
• Functional Keywords: serine protease, zymogen, hydrolase
• Biological source: Homo sapiens (human)
• Cellular location: Secreted: P48052
• Total number of polymer chains: 1
• Total formula weight: 45072.07

Authors

Garcia-Saez, I.,Reverte, D.,Vendrell, J.,Aviles, F.X.,Coll, M. (deposition date: 1997-11-03, release date: 1999-01-13, Last modification date: 2024-11-20)

Primary citation

Garcia-Saez, I.,Reverter, D.,Vendrell, J.,Aviles, F.X.,Coll, M.
The three-dimensional structure of human procarboxypeptidase A2. Deciphering the basis of the inhibition, activation and intrinsic activity of the zymogen.
EMBO J., 16:6906-6913, 1997

PubMed Abstract: The three-dimensional structure of human procarboxypeptidase A2 has been determined using X-ray crystallography at 1.8 A resolution. This is the first detailed structural report of a human pancreatic carboxypeptidase and of its zymogen. Human procarboxypeptidase A2 is formed by a pro-segment of 96 residues, which inhibits the enzyme, and a carboxypeptidase moiety of 305 residues. The pro-enzyme maintains the general fold when compared with other non-human counterparts. The globular part of the pro-segment docks into the enzyme moiety and shields the S2-S4 substrate binding sites, promoting inhibition. Interestingly, important differences are found in the pro-segment which allow the identification of the structural determinants of the diverse activation behaviours of procarboxypeptidases A1, B and A2, particularly of the latter. The benzylsuccinic inhibitor is able to diffuse into the active site of procarboxypeptidase A2 in the crystals. The structure of the zymogen-inhibitor complex has been solved at 2.2 A resolution. The inhibitor enters the active site through a channel formed at the interface between the pro-segment and the enzyme regions and interacts with important elements of the active site. The derived structural features explain the intrinsic activity of A1/A2 pro-enzymes for small substrates.

PubMed: 9384570
DOI: 10.1093/emboj/16.23.6906

Experimental method

X-RAY DIFFRACTION (1.8 Å)