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[[Image:2v4b.jpg|left|200px]]


{{Structure
==Crystal Structure of Human ADAMTS-1 catalytic Domain and Cysteine- Rich Domain (apo-form)==
|PDB= 2v4b |SIZE=350|CAPTION= <scene name='initialview01'>2v4b</scene>, resolution 2.00&Aring;
<StructureSection load='2v4b' size='340' side='right'caption='[[2v4b]], [[Resolution|resolution]] 2.00&Aring;' scene=''>
|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>
== Structural highlights ==
|LIGAND= <scene name='pdbligand=ZN:ZINC+ION'>ZN</scene>, <scene name='pdbligand=CD:CADMIUM+ION'>CD</scene>, <scene name='pdbligand=NI:NICKEL+(II)+ION'>NI</scene>, <scene name='pdbligand=MG:MAGNESIUM+ION'>MG</scene> and <scene name='pdbligand=NA:SODIUM ION'>NA</scene>
<table><tr><td colspan='2'>[[2v4b]] is a 2 chain structure with sequence from [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2V4B OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=2V4B FirstGlance]. <br>
|ACTIVITY=  
</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 2&#8491;</td></tr>
|GENE=  
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><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></td></tr>
}}
<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=2v4b FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2v4b OCA], [https://pdbe.org/2v4b PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=2v4b RCSB], [https://www.ebi.ac.uk/pdbsum/2v4b PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=2v4b ProSAT]</span></td></tr>
</table>
== Function ==
[https://www.uniprot.org/uniprot/ATS1_HUMAN ATS1_HUMAN] Cleaves aggrecan, a cartilage proteoglycan, and may be involved in its turnover (By similarity). Has angiogenic inhibitor activity. Active metalloprotease, which may be associated with various inflammatory processes as well as development of cancer cachexia. May play a critical role in follicular rupture.<ref>PMID:10438512</ref>  
== Evolutionary Conservation ==
[[Image:Consurf_key_small.gif|200px|right]]
Check<jmol>
  <jmolCheckbox>
    <scriptWhenChecked>; select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/v4/2v4b_consurf.spt"</scriptWhenChecked>
    <scriptWhenUnchecked>script /wiki/extensions/Proteopedia/spt/initialview03.spt</scriptWhenUnchecked>
    <text>to colour the structure by Evolutionary Conservation</text>
  </jmolCheckbox>
</jmol>, as determined by [http://consurfdb.tau.ac.il/ ConSurfDB]. You may read the [[Conservation%2C_Evolutionary|explanation]] of the method and the full data available from [http://bental.tau.ac.il/new_ConSurfDB/main_output.php?pdb_ID=2v4b ConSurf].
<div style="clear:both"></div>
<div style="background-color:#fffaf0;">
== Publication Abstract from PubMed ==
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.


'''CRYSTAL STRUCTURE OF HUMAN ADAMTS-1 CATALYTIC DOMAIN AND CYSTEINE-RICH DOMAIN (APO-FORM)'''
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<ref>PMID:17897672</ref>


From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
</div>
<div class="pdbe-citations 2v4b" style="background-color:#fffaf0;"></div>


==Overview==
==See Also==
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.
*[[A Disintegrin And Metalloproteinase 3D structures|A Disintegrin And Metalloproteinase 3D structures]]
 
== References ==
==About this Structure==
<references/>
2V4B is a [[Single protein]] structure of sequence from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2V4B OCA].
__TOC__
 
</StructureSection>
==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:[http://www.ncbi.nlm.nih.gov/pubmed/17897672 17897672]
[[Category: Homo sapiens]]
[[Category: Homo sapiens]]
[[Category: Single protein]]
[[Category: Large Structures]]
[[Category: Abbott, W M.]]
[[Category: Abbott WM]]
[[Category: Flavell, L.]]
[[Category: Flavell L]]
[[Category: Gerhardt, S.]]
[[Category: Gerhardt S]]
[[Category: Hargreaves, D.]]
[[Category: Hargreaves D]]
[[Category: Hassall, G.]]
[[Category: Hassall G]]
[[Category: Hawtin, P.]]
[[Category: Hawtin P]]
[[Category: Mccall, E.]]
[[Category: McCall E]]
[[Category: Minshull, C.]]
[[Category: Minshull C]]
[[Category: Parker, A E.]]
[[Category: Parker AE]]
[[Category: Pauptit, R A.]]
[[Category: Pauptit RA]]
[[Category: Ting, A.]]
[[Category: Ting A]]
[[Category: CD]]
[[Category: MG]]
[[Category: NA]]
[[Category: NI]]
[[Category: ZN]]
[[Category: adamts-1]]
[[Category: cleavage on pair of basic residue]]
[[Category: extracellular matrix]]
[[Category: glycoprotein]]
[[Category: heparin-binding]]
[[Category: hydrolase]]
[[Category: metal-binding]]
[[Category: metalloprotease]]
[[Category: metalloproteinase]]
[[Category: metzincin]]
[[Category: polymorphism]]
[[Category: protease]]
[[Category: zinc]]
[[Category: zymogen]]
 
''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Mar 20 18:43:14 2008''

Latest revision as of 08:31, 17 October 2024

Crystal Structure of Human ADAMTS-1 catalytic Domain and Cysteine- Rich Domain (apo-form)Crystal Structure of Human ADAMTS-1 catalytic Domain and Cysteine- Rich Domain (apo-form)

Structural highlights

2v4b is a 2 chain structure with sequence from Homo sapiens. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Method:X-ray diffraction, Resolution 2Å
Ligands:, , , ,
Resources:FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Function

ATS1_HUMAN Cleaves aggrecan, a cartilage proteoglycan, and may be involved in its turnover (By similarity). Has angiogenic inhibitor activity. Active metalloprotease, which may be associated with various inflammatory processes as well as development of cancer cachexia. May play a critical role in follicular rupture.[1]

Evolutionary Conservation

Check, as determined by ConSurfDB. You may read the explanation of the method and the full data available from ConSurf.

Publication Abstract from PubMed

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.

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[2]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

See Also

References

  1. ↑ Vazquez F, Hastings G, Ortega MA, Lane TF, Oikemus S, Lombardo M, Iruela-Arispe ML. METH-1, a human ortholog of ADAMTS-1, and METH-2 are members of a new family of proteins with angio-inhibitory activity. J Biol Chem. 1999 Aug 13;274(33):23349-57. PMID:10438512
  2. ↑ Gerhardt S, Hassall G, Hawtin P, McCall E, Flavell L, Minshull C, Hargreaves D, Ting A, Pauptit RA, Parker AE, Abbott WM. Crystal structures of human ADAMTS-1 reveal a conserved catalytic domain and a disintegrin-like domain with a fold homologous to cysteine-rich domains. J Mol Biol. 2007 Nov 2;373(4):891-902. Epub 2007 Aug 2. PMID:17897672 doi:10.1016/j.jmb.2007.07.047

2v4b, resolution 2.00Å

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