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{{STRUCTURE_3vn4|  PDB=3vn4  |  SCENE=  }}
==Crystal structure of the exosite-containing fragment of human ADAMTS13 (P475S mutant)==
===Crystal structure of the exosite-containing fragment of human ADAMTS13 (P475S mutant)===
<StructureSection load='3vn4' size='340' side='right' caption='[[3vn4]], [[Resolution|resolution]] 2.80&Aring;' scene=''>
{{ABSTRACT_PUBMED_19880749}}
== Structural highlights ==
 
<table><tr><td colspan='2'>[[3vn4]] is a 1 chain structure with 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=3VN4 OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=3VN4 FirstGlance]. <br>
==Disease==
</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=BGC:BETA-D-GLUCOSE'>BGC</scene>, <scene name='pdbligand=BMA:BETA-D-MANNOSE'>BMA</scene>, <scene name='pdbligand=NAG:N-ACETYL-D-GLUCOSAMINE'>NAG</scene>, <scene name='pdbligand=FUC:ALPHA-L-FUCOSE'>FUC</scene></td></tr>
[[http://www.uniprot.org/uniprot/ATS13_HUMAN ATS13_HUMAN]] Defects in ADAMTS13 are the cause of thrombotic thrombocytopenic purpura congenital (TTP) [MIM:[http://omim.org/entry/274150 274150]]; also known as Upshaw-Schulman syndrome (USS). A hematologic disease characterized by hemolytic anemia with fragmentation of erythrocytes, thrombocytopenia, diffuse and non-focal neurologic findings, decreased renal function and fever.<ref>PMID:11586351</ref><ref>PMID:12181489</ref><ref>PMID:12393505</ref><ref>PMID:12614216</ref><ref>PMID:12753286</ref><ref>PMID:14512317</ref><ref>PMID:14563640</ref><ref>PMID:15126318</ref><ref>PMID:15009458</ref><ref>PMID:15327386</ref><ref>PMID:16160007</ref><ref>PMID:16453338</ref><ref>PMID:16796708</ref><ref>PMID:16449289</ref><ref>PMID:16807643</ref><ref>PMID:17003922</ref><ref>PMID:18443791</ref><ref>PMID:19055667</ref><ref>PMID:19116307</ref><ref>PMID:22075512</ref>  
<tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[3ghm|3ghm]], [[3ghn|3ghn]]</td></tr>
<tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">ADAMTS13 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 Homo sapiens])</td></tr>
<tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[http://en.wikipedia.org/wiki/ADAMTS13_endopeptidase ADAMTS13 endopeptidase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=3.4.24.87 3.4.24.87] </span></td></tr>
<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=3vn4 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3vn4 OCA], [http://www.rcsb.org/pdb/explore.do?structureId=3vn4 RCSB], [http://www.ebi.ac.uk/pdbsum/3vn4 PDBsum]</span></td></tr>
</table>
== Disease ==
[[http://www.uniprot.org/uniprot/ATS13_HUMAN ATS13_HUMAN]] Defects in ADAMTS13 are the cause of thrombotic thrombocytopenic purpura congenital (TTP) [MIM:[http://omim.org/entry/274150 274150]]; also known as Upshaw-Schulman syndrome (USS). A hematologic disease characterized by hemolytic anemia with fragmentation of erythrocytes, thrombocytopenia, diffuse and non-focal neurologic findings, decreased renal function and fever.<ref>PMID:11586351</ref> <ref>PMID:12181489</ref> <ref>PMID:12393505</ref> <ref>PMID:12614216</ref> <ref>PMID:12753286</ref> <ref>PMID:14512317</ref> <ref>PMID:14563640</ref> <ref>PMID:15126318</ref> <ref>PMID:15009458</ref> <ref>PMID:15327386</ref> <ref>PMID:16160007</ref> <ref>PMID:16453338</ref> <ref>PMID:16796708</ref> <ref>PMID:16449289</ref> <ref>PMID:16807643</ref> <ref>PMID:17003922</ref> <ref>PMID:18443791</ref> <ref>PMID:19055667</ref> <ref>PMID:19116307</ref> <ref>PMID:22075512</ref>
== Function ==
[[http://www.uniprot.org/uniprot/ATS13_HUMAN ATS13_HUMAN]] Cleaves the vWF multimers in plasma into smaller forms.
<div style="background-color:#fffaf0;">
== Publication Abstract from PubMed ==
ADAMTS13 specifically cleaves plasma von Willebrand factor (VWF) and thereby controls VWF-mediated platelet thrombus formation. Severe deficiencies in ADAMTS13 can cause life-threatening thrombotic thrombocytopenic purpura. Here, we determined 2 crystal structures of ADAMTS13-DTCS (residues 287-685), an exosite-containing human ADAMTS13 fragment, at 2.6-A and 2.8-A resolution. The structures revealed folding similarities between the disintegrin-like (D) domain and the N-terminal portion of the cysteine-rich domain (designated the C(A) domain). The spacer (S) domain forms a globular functional unit with a 10-stranded beta-sandwich fold that has multiple interaction sites with the C(A) domain. We expressed 25 structure-based mutants of ADAMTS13-MDTCS (residues 75-685) and measured their enzymatic activity. We identified 3 VWF-binding exosites on the linearly aligned discontinuous surfaces of the D, C(A), and S domains traversing the W-shaped molecule. Since the MDTCS domains are conserved among ADAMTS family proteins, the structural framework of the multiple enzyme-substrate interactions identified in the ADAMTS13-VWF system provides the basis for a common substrate recognition mode in this class of proteinases.


==Function==
Crystal structures of the noncatalytic domains of ADAMTS13 reveal multiple discontinuous exosites for von Willebrand factor.,Akiyama M, Takeda S, Kokame K, Takagi J, Miyata T Proc Natl Acad Sci U S A. 2009 Nov 17;106(46):19274-9. Epub 2009 Oct 30. PMID:19880749<ref>PMID:19880749</ref>
[[http://www.uniprot.org/uniprot/ATS13_HUMAN ATS13_HUMAN]] Cleaves the vWF multimers in plasma into smaller forms.


==About this Structure==
From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
[[3vn4]] is a 1 chain structure with 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=3VN4 OCA].
</div>


==See Also==
==See Also==
*[[A Disintegrin And Metalloproteinase|A Disintegrin And Metalloproteinase]]
*[[A Disintegrin And Metalloproteinase|A Disintegrin And Metalloproteinase]]
 
== References ==
==Reference==
<references/>
<ref group="xtra">PMID:019880749</ref><references group="xtra"/><references/>
__TOC__
</StructureSection>
[[Category: ADAMTS13 endopeptidase]]
[[Category: ADAMTS13 endopeptidase]]
[[Category: Homo sapiens]]
[[Category: Homo sapiens]]
[[Category: Akiyama, M.]]
[[Category: Akiyama, M]]
[[Category: Kokame, K.]]
[[Category: Kokame, K]]
[[Category: Miyata, T.]]
[[Category: Miyata, T]]
[[Category: Nakayama, D.]]
[[Category: Nakayama, D]]
[[Category: Takagi, J.]]
[[Category: Takagi, J]]
[[Category: Takeda, S.]]
[[Category: Takeda, S]]
[[Category: Hydrolase]]
[[Category: Hydrolase]]
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