2jih | pdb_00002jih

CRYSTAL STRUCTURE OF HUMAN ADAMTS-1 CATALYTIC DOMAIN AND CYSTEINE-RICH DOMAIN (COMPLEX-FORM)

File:2jih.jpg

spinqualitylabelsall models 2jih, resolution 2.1Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D

Overview

The ADAMTS (a disintegrin-like and metalloproteinase domain with, thrombospondin type I motifs) family of proteases plays a role in, pathological conditions including arthritis, cancer, thrombotic, thrombocytopenic purpura and the Ehlers-Danlos type VIIC and, Weill-Marchesani genetic syndromes. Here, we report the first crystal, structures for a member of the ADAMTS family, ADAMTS-1. Originally cloned, as an inflammation-associated gene, ADAMTS-1 has been shown to be involved, in tissue remodelling, wound healing and angiogenesis. The crystal, structures contain catalytic and disintegrin-like domains, both in the, inhibitor-free form and in complex with the inhibitor marimastat. The, overall fold of the catalytic domain is similar to related zinc, metalloproteinases such as matrix metalloproteinases and ADAMs (a, disintegrin and metalloproteinases). The active site contains the expected, organisation of residues to coordinate zinc but has a much larger S1', selectivity pocket than ADAM33. The structure also unexpectedly reveals a, double calcium-binding site. Also surprisingly, the previously named, disintegrin-like domain showed no structural homology to the disintegrin, domains of other metalloproteinases such as ADAM10 but is instead very, similar in structure to the cysteine-rich domains of other, metalloproteinases. Thus, this study suggests that the D (for, disintegrin-like) in the nomenclature of ADAMTS enzymes is likely to be a, misnomer. The ADAMTS-1 cysteine-rich domain stacks against the active, site, suggesting a possible regulatory role.

About this Structure

2JIH is a Single protein structure of sequence from Homo sapiens with ZN, CD, NI, MG, NA and 097 as ligands. Known structural/functional Sites: AC1, AC2, AC3, AC4, AC5, AC6, AC7, AC8, AC9, BC1, BC2, BC3, BC4, BC5, BC6, BC7, BC8, BC9, CC1, CC2, CC3, CC4, CC7, CC8, CC9, DC1, DC2, DC3 and DC4. Full crystallographic information is available from OCA.

Reference

Crystal structures of human ADAMTS-1 reveal a conserved catalytic domain and a disintegrin-like domain with a fold homologous to cysteine-rich domains., Gerhardt S, Hassall G, Hawtin P, McCall E, Flavell L, Minshull C, Hargreaves D, Ting A, Pauptit RA, Parker AE, Abbott WM, J Mol Biol. 2007 Nov 2;373(4):891-902. Epub 2007 Aug 2. PMID:17897672

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