The three-dimensional structures of tick carboxypeptidase inhibitor in complex with A/B carboxypeptidases reveal a novel double-headed binding mode

Arolas, Joan L., Popowicz, Grzegorz M., Lorenzo, Julia, Sommerhoff, Christian P., Huber, Robert, Aviles, Francesc X. and Holak, Tad A. 2005. The three-dimensional structures of tick carboxypeptidase inhibitor in complex with A/B carboxypeptidases reveal a novel double-headed binding mode. Journal of Molecular Biology 350 (3) , pp. 489-498. 10.1016/j.jmb.2005.05.015

Full text not available from this repository.

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 Å and at 2.0 Å 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 α-helix followed by a small twisted antiparallel β-sheet, show a high level of structural homology to proteins of the β-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.

Item Type:	Article
Date Type:	Publication
Status:	Published
Schools:	Biosciences
Subjects:	Q Science > QR Microbiology
Uncontrolled Keywords:	metallo-carboxypeptidase; carboxypeptidase inhibitor; inhibitor–enzyme complex; crystal structure; pro-fibrinolytic drug
Publisher:	Elsevier
ISSN:	0022-2836
Last Modified:	24 Jun 2017 11:00
URI:	https://orca.cardiff.ac.uk/id/eprint/70007

Citation Data

Cited 54 times in Scopus. View in Scopus. Powered By Scopus® Data

Actions (repository staff only)

Edit Item