1dtd

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File:1dtd.gif


1dtd, resolution 1.65Å

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

OverviewOverview

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.

About this StructureAbout this Structure

1DTD is a Protein complex structure of sequences from Hirudo medicinalis and Homo sapiens with and as ligands. Active as Peptidyl-dipeptidase A, with EC number 3.4.15.1 Full crystallographic information is available from OCA.

ReferenceReference

Structure of a novel leech carboxypeptidase inhibitor determined free in solution and in complex with human carboxypeptidase A2., Reverter D, Fernandez-Catalan C, Baumgartner R, Pfander R, Huber R, Bode W, Vendrell J, Holak TA, Aviles FX, Nat Struct Biol. 2000 Apr;7(4):322-8. PMID:10742178

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