2v4b

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{{STRUCTURE_2v4b| PDB=2v4b | SCENE= }}
{{STRUCTURE_2v4b| PDB=2v4b | SCENE= }}
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'''CRYSTAL STRUCTURE OF HUMAN ADAMTS-1 CATALYTIC DOMAIN AND CYSTEINE-RICH DOMAIN (APO-FORM)'''
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===CRYSTAL STRUCTURE OF HUMAN ADAMTS-1 CATALYTIC DOMAIN AND CYSTEINE-RICH DOMAIN (APO-FORM)===
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==Overview==
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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.
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{{ABSTRACT_PUBMED_17897672}}
==About this Structure==
==About this Structure==
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[[Category: Zinc]]
[[Category: Zinc]]
[[Category: Zymogen]]
[[Category: Zymogen]]
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''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Mon Jul 28 20:01:03 2008''

Revision as of 17:01, 28 July 2008

Image:2v4b.png

Template:STRUCTURE 2v4b

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

Template:ABSTRACT PUBMED 17897672

About this Structure

2V4B is a Single protein structure of sequence from Homo sapiens. 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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