1ZLI

Crystal structure of the tick carboxypeptidase inhibitor in complex with human carboxypeptidase B

Summary for 1ZLI

• Entry DOI: 10.2210/pdb1zli/pdb
• Related: 1ZLH
• Descriptor: Carboxypeptidase B, carboxypeptidase inhibitor, ZINC ION, ... (4 entities in total)
• Functional Keywords: inhibitor-metallocarboxypeptidase complex, beta-defensin fold (tci), eight-stranded twisted beta-sheet surrounded by eight alpha-helices (cpb), hydrolase-hydrolase inhibitor complex, hydrolase/hydrolase inhibitor
• Biological source: Homo sapiens (human); More
• Cellular location: Secreted : P15086
• Total number of polymer chains: 2
• Total formula weight: 43137.98

Authors

Arolas, J.L.,Popowicz, G.M.,Lorenzo, J.,Sommerhoff, C.P.,Huber, R.,Aviles, F.X.,Holak, T.A. (deposition date: 2005-05-06, release date: 2005-07-05, Last modification date: 2024-10-16)

Primary citation

Arolas, J.L.,Popowicz, G.M.,Lorenzo, J.,Sommerhoff, C.P.,Huber, R.,Aviles, F.X.,Holak, T.A.
The Three-Dimensional Structures of Tick Carboxypeptidase Inhibitor in Complex with A/B Carboxypeptidases Reveal a Novel Double-headed Binding Mode
J.Mol.Biol., 350:489-498, 2005

PubMed Abstract: The tick carboxypeptidase inhibitor (TCI) is a proteinaceous inhibitor of metallo-carboxypeptidases present in the blood-sucking tick Rhipicephalus bursa. The three-dimensional crystal structures of recombinant TCI bound to bovine carboxypeptidase A and to human carboxypeptidase B have been determined and refined at 1.7 A and at 2.0 A resolution, respectively. TCI consists of two domains that are structurally similar despite the low degree of sequence homology. The domains, each consisting of a short alpha-helix followed by a small twisted antiparallel beta-sheet, show a high level of structural homology to proteins of the beta-defensin-fold family. TCI anchors to the surface of mammalian carboxypeptidases in a double-headed manner not previously seen for carboxypeptidase inhibitors: the last three carboxy-terminal amino acid residues interact with the active site of the enzyme in a way that mimics substrate binding, and the N-terminal domain binds to an exosite distinct from the active-site groove. The structures of these complexes should prove valuable in the applications of TCI as a thrombolytic drug and as a basis for the design of novel bivalent carboxypeptidase inhibitors.

PubMed: 15961103
DOI: 10.1016/j.jmb.2005.05.015

Experimental method

X-RAY DIFFRACTION (2.09 Å)