1DTD

CRYSTAL STRUCTURE OF THE COMPLEX BETWEEN THE LEECH CARBOXYPEPTIDASE INHIBITOR AND THE HUMAN CARBOXYPEPTIDASE A2 (LCI-CPA2)

Summary for 1DTD

• Entry DOI: 10.2210/pdb1dtd/pdb
• Descriptor: CARBOXYPEPTIDASE A2, METALLOCARBOXYPEPTIDASE INHIBITOR, ZINC ION, ... (5 entities in total)
• Functional Keywords: carboxypeptidase a2, leech carboxypeptidase inhibitor, hydrolase-hydrolase inhibitor complex, hydrolase/hydrolase inhibitor
• Biological source: Homo sapiens (human); More
• Cellular location: Secreted: P48052
• Total number of polymer chains: 2
• Total formula weight: 40661.13

Authors

Reverter, D.,Fernandez-Catalan, C.,Bode, W.,Holak, T.A.,Aviles, F.X. (deposition date: 2000-01-12, release date: 2000-07-12, Last modification date: 2024-10-09)

Primary citation

Reverter, D.,Fernandez-Catalan, C.,Baumgartner, R.,Pfander, R.,Huber, R.,Bode, W.,Vendrell, J.,Holak, T.A.,Aviles, F.X.
Structure of a novel leech carboxypeptidase inhibitor determined free in solution and in complex with human carboxypeptidase A2.
Nat.Struct.Biol., 7:322-328, 2000

PubMed Abstract: Leech carboxypeptidase inhibitor (LCI) is a novel protein inhibitor present in the medicinal leech Hirudo medicinalis. The structures of LCI free and bound to carboxypeptidase A2 (CPA2)have been determined by NMR and X-ray crystallography, respectively. The LCI structure defines a new protein motif that comprises a five-stranded antiparallel beta-sheet and one short alpha-helix. This structure is preserved in the complex with human CPA2 in the X-ray structure, where the contact regions between the inhibitor and the protease are defined. The C-terminal tail of LCI becomes rigid upon binding the protease as shown in the NMR relaxation studies, and it interacts with the carboxypeptidase in a substrate-like manner. The homology between the C-terminal tails of LCI and the potato carboxypeptidase inhibitor represents a striking example of convergent evolution dictated by the target protease. These new structures are of biotechnological interest since they could elucidate the control mechanism of metallo-carboxypeptidases and could be used as lead compounds for the search of fibrinolytic drugs.

PubMed: 10742178
DOI: 10.1038/74092

Experimental method

X-RAY DIFFRACTION (1.65 Å)