1aye
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| , resolution 1.8Å | |||||||
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| Sites: | |||||||
| Ligands: | |||||||
| Activity: | Carboxypeptidase A2, with EC number 3.4.17.15 | ||||||
| Coordinates: | save as pdb, mmCIF, xml | ||||||
HUMAN PROCARBOXYPEPTIDASE A2
OverviewOverview
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.
About this StructureAbout this Structure
1AYE is a Single protein structure of sequence from Homo sapiens. Full crystallographic information is available from OCA.
ReferenceReference
The three-dimensional structure of human procarboxypeptidase A2. Deciphering the basis of the inhibition, activation and intrinsic activity of the zymogen., Garcia-Saez I, Reverter D, Vendrell J, Aviles FX, Coll M, EMBO J. 1997 Dec 1;16(23):6906-13. PMID:9384570
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