2v4b: Difference between revisions

Revision as of 18:12, 4 May 2008

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

OverviewOverview

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 StructureAbout this Structure

2V4B is a Single protein structure of sequence from Homo sapiens. Full crystallographic information is available from OCA.

ReferenceReference

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 Page seeded by OCA on Sun May 4 18:12:11 2008

Proteopedia Page Contributors and Editors (what is this?)Proteopedia Page Contributors and Editors (what is this?)

OCA

@@ Line 1: / Line 1: @@
 [[Image:2v4b.jpg|left|200px]]
- {{Structure
+<!--
-|PDB= 2v4b |SIZE=350|CAPTION= <scene name='initialview01'>2v4b</scene>, resolution 2.00&Aring;
+The line below this paragraph, containing "STRUCTURE_2v4b", creates the "Structure Box" on the page.
-|SITE= <scene name='pdbsite=AC1:Zn+Binding+Site+For+Chain+A'>AC1</scene>, <scene name='pdbsite=AC2:Zn+Binding+Site+For+Chain+B'>AC2</scene>, <scene name='pdbsite=AC3:Cd+Binding+Site+For+Chain+A'>AC3</scene>, <scene name='pdbsite=AC4:Cd+Binding+Site+For+Chain+A'>AC4</scene>, <scene name='pdbsite=AC5:Ni+Binding+Site+For+Chain+A'>AC5</scene>, <scene name='pdbsite=AC6:Ni+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+B'>AC8</scene>, <scene name='pdbsite=AC9:Ni+Binding+Site+For+Chain+B'>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:Ni+Binding+Site+For+Chain+A'>BC3</scene>, <scene name='pdbsite=BC4:Ni+Binding+Site+For+Chain+A'>BC4</scene>, <scene name='pdbsite=BC5:Mg+Binding+Site+For+Chain+A'>BC5</scene>, <scene name='pdbsite=BC6:Ni+Binding+Site+For+Chain+A'>BC6</scene>, <scene name='pdbsite=BC7:Ni+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:Mg+Binding+Site+For+Chain+B'>CC1</scene>, <scene name='pdbsite=CC2:Ni+Binding+Site+For+Chain+B'>CC2</scene>, <scene name='pdbsite=CC3:Ni+Binding+Site+For+Chain+B'>CC3</scene>, <scene name='pdbsite=CC4:Ni+Binding+Site+For+Chain+B'>CC4</scene>, <scene name='pdbsite=CC5:Mg+Binding+Site+For+Chain+A'>CC5</scene>, <scene name='pdbsite=CC6:Na+Binding+Site+For+Chain+A'>CC6</scene>, <scene name='pdbsite=CC7:Na+Binding+Site+For+Chain+B'>CC7</scene>, <scene name='pdbsite=CC8:Na+Binding+Site+For+Chain+A'>CC8</scene> and <scene name='pdbsite=CC9:Na+Binding+Site+For+Chain+B'>CC9</scene>
+You may change the PDB parameter (which sets the PDB file loaded into the applet)
-|LIGAND= <scene name='pdbligand=CD:CADMIUM+ION'>CD</scene>, <scene name='pdbligand=MG:MAGNESIUM+ION'>MG</scene>, <scene name='pdbligand=NA:SODIUM+ION'>NA</scene>, <scene name='pdbligand=NI:NICKEL+(II)+ION'>NI</scene>, <scene name='pdbligand=ZN:ZINC+ION'>ZN</scene>
+or the SCENE parameter (which sets the initial scene displayed when the page is loaded),
-|ACTIVITY=
+or leave the SCENE parameter empty for the default display.
-|GENE=
+-->
-|DOMAIN=
+{{STRUCTURE_2v4b|  PDB=2v4b  |  SCENE=  }}
-|RELATEDENTRY=[[2jih|2JIH]]
-|RESOURCES=<span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=2v4b FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2v4b OCA], [http://www.ebi.ac.uk/pdbsum/2v4b PDBsum], [http://www.rcsb.org/pdb/explore.do?structureId=2v4b RCSB]</span>
-}}
 '''CRYSTAL STRUCTURE OF HUMAN ADAMTS-1 CATALYTIC DOMAIN AND CYSTEINE-RICH DOMAIN (APO-FORM)'''
@@ Line 36: / Line 33: @@
 [[Category: Pauptit, R A.]]
 [[Category: Ting, A.]]
-[[Category: adamts-1]]
+[[Category: Adamts-1]]
-[[Category: cleavage on pair of basic residue]]
+[[Category: Cleavage on pair of basic residue]]
-[[Category: extracellular matrix]]
+[[Category: Extracellular matrix]]
-[[Category: glycoprotein]]
+[[Category: Glycoprotein]]
-[[Category: heparin-binding]]
+[[Category: Heparin-binding]]
-[[Category: hydrolase]]
+[[Category: Hydrolase]]
-[[Category: metal-binding]]
+[[Category: Metal-binding]]
-[[Category: metalloprotease]]
+[[Category: Metalloprotease]]
-[[Category: metalloproteinase]]
+[[Category: Metalloproteinase]]
-[[Category: metzincin]]
+[[Category: Metzincin]]
-[[Category: polymorphism]]
+[[Category: Polymorphism]]
-[[Category: protease]]
+[[Category: Protease]]
-[[Category: zinc]]
+[[Category: Zinc]]
-[[Category: zymogen]]
+[[Category: Zymogen]]
+''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Sun May  4 18:12:11 2008''
-''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Mon Mar 31 05:08:24 2008''