2jih: Difference between revisions

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.

2JIH is a [http://en.wikipedia.org/wiki/Single_protein Single protein] structure of sequence from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens] with <scene name='pdbligand=ZN:'>ZN</scene>, <scene name='pdbligand=CD:'>CD</scene>, <scene name='pdbligand=NI:'>NI</scene>, <scene name='pdbligand=MG:'>MG</scene>, <scene name='pdbligand=NA:'>NA</scene> and <scene name='pdbligand=097:'>097</scene> as [http://en.wikipedia.org/wiki/ligands ligands]. Known structural/functional Sites: <scene name='pdbsite=AC1:097 Binding Site For Chain A'>AC1</scene>, <scene name='pdbsite=AC2:097 Binding Site For Chain B'>AC2</scene>, <scene name='pdbsite=AC3:Zn Binding Site For Chain A'>AC3</scene>, <scene name='pdbsite=AC4:Zn Binding Site For Chain B'>AC4</scene>, <scene name='pdbsite=AC5:Cd Binding Site For Chain A'>AC5</scene>, <scene name='pdbsite=AC6:Cd Binding Site For Chain A'>AC6</scene>, <scene name='pdbsite=AC7:Ni Binding Site For Chain A'>AC7</scene>, <scene name='pdbsite=AC8:Cd Binding Site For Chain A'>AC8</scene>, <scene name='pdbsite=AC9:Cd Binding Site For Chain A'>AC9</scene>, <scene name='pdbsite=BC1:Cd Binding Site For Chain B'>BC1</scene>, <scene name='pdbsite=BC2:Ni Binding Site For Chain B'>BC2</scene>, <scene name='pdbsite=BC3:Cd Binding Site For Chain B'>BC3</scene>, <scene name='pdbsite=BC4:Ni Binding Site For Chain B'>BC4</scene>, <scene name='pdbsite=BC5:Ni Binding Site For Chain B'>BC5</scene>, <scene name='pdbsite=BC6:Ni Binding Site For Chain A'>BC6</scene>, <scene name='pdbsite=BC7:Mg Binding Site For Chain A'>BC7</scene>, <scene name='pdbsite=BC8:Ni Binding Site For Chain A'>BC8</scene>, <scene name='pdbsite=BC9:Ni Binding Site For Chain A'>BC9</scene>, <scene name='pdbsite=CC1:Ni Binding Site For Chain A'>CC1</scene>, <scene name='pdbsite=CC2:Ni Binding Site For Chain A'>CC2</scene>, <scene name='pdbsite=CC3:Mg Binding Site For Chain B'>CC3</scene>, <scene name='pdbsite=CC4:Ni Binding Site For Chain B'>CC4</scene>, <scene name='pdbsite=CC7:Na Binding Site For Chain A'>CC7</scene>, <scene name='pdbsite=CC8:Na Binding Site For Chain A'>CC8</scene>, <scene name='pdbsite=CC9:Na Binding Site For Chain A'>CC9</scene>, <scene name='pdbsite=DC1:Na Binding Site For Chain B'>DC1</scene>, <scene name='pdbsite=DC2:Na Binding Site For Chain B'>DC2</scene>, <scene name='pdbsite=DC3:Ni Binding Site For Chain A'>DC3</scene> and <scene name='pdbsite=DC4:Mg Binding Site For Chain A'>DC4</scene>. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2JIH OCA].  

[[Category: Abbott, W.M.]]

[[Category: Parker, A.E.]]

[[Category: Pauptit, R.A.]]

''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Wed Jan 23 11:05:45 2008''