4BD9

Structure of the complex between SmCI and human carboxypeptidase A4

Summary for 4BD9

• Entry DOI: 10.2210/pdb4bd9/pdb
• Related: 2BO9 2BOA 4A94
• Descriptor: CARBOXYPEPTIDASE A4, CARBOXYPEPTIDASE INHIBITOR SMCI, ZINC ION, ... (4 entities in total)
• Functional Keywords: hydrolase-hydrolase inhibitor complex, serine protease inhibitor, hydrolase/hydrolase inhibitor
• Biological source: HOMO SAPIENS (HUMAN); More
• Cellular location: Secreted (By similarity): Q9UI42
• Total number of polymer chains: 2
• Total formula weight: 53541.04

Authors

Alonso-del-Ribero, M.,Reytor, M.L.,Trejo, S.A.,Chavez, M.A.,Aviles, F.X.,Reverter, D. (deposition date: 2012-10-05, release date: 2013-07-17, Last modification date: 2024-11-13)

Primary citation

Alonso Del Rivero, M.,Reytor, M.L.,Trejo, S.A.,Chavez, M.A.,Aviles, F.X.,Reverter, D.
A Noncanonical Mechanism of Carboxypeptidase Inhibition Revealed by the Crystal Structure of the Tri-Kunitz Smci in Complex with Human Cpa4.
Structure, 21:1118-, 2013

PubMed Abstract: The crystal structure of SmCI (Sabellastarte magnifica carboxypeptidase inhibitor) has been determined in complex with human carboxypeptidase A4 (hCPA4). SmCI is composed by three BPTI/Kunitz domains, each one displaying high structural homology and functionality with serine protease inhibitors. Moreover, SmCI possesses a distinctive capability to inhibit metallo-carboxypeptidases, constituting a bifunctional metallocarboxy- and serine protease inhibitor. The structure of the 1:1 complex of SmCI with hCPA4 reveals a noncanonical mechanism of carboxypeptidase inhibition, which surprisingly occurs mainly via the N-terminal segment, which penetrates into the active site groove of the enzyme. Mutagenesis and biochemical analysis confirm the major role of the N-terminal segment in the inhibition of carboxypeptidases. SmCI represents a tri-Kunitz serine protease inhibitor adapted to inhibit metallo-carboxypeptidases and discloses an unusual mechanism of inhibition by the N-terminal segment, emulating the "classical" C-terminal substrate-like inhibition.

PubMed: 23746805
DOI: 10.1016/J.STR.2013.04.021

Experimental method

X-RAY DIFFRACTION (2.2 Å)