3vn4

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Current revision (06:10, 31 July 2024) (edit) (undo)
 
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<table><tr><td colspan='2'>[[3vn4]] is a 1 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=3VN4 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=3VN4 FirstGlance]. <br>
<table><tr><td colspan='2'>[[3vn4]] is a 1 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=3VN4 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=3VN4 FirstGlance]. <br>
</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 2.8&#8491;</td></tr>
</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 2.8&#8491;</td></tr>
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<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=BGC:BETA-D-GLUCOSE'>BGC</scene>, <scene name='pdbligand=BMA:BETA-D-MANNOSE'>BMA</scene>, <scene name='pdbligand=FUC:ALPHA-L-FUCOSE'>FUC</scene>, <scene name='pdbligand=NAG:N-ACETYL-D-GLUCOSAMINE'>NAG</scene></td></tr>
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<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=BGC:BETA-D-GLUCOSE'>BGC</scene>, <scene name='pdbligand=FUC:ALPHA-L-FUCOSE'>FUC</scene>, <scene name='pdbligand=MAN:ALPHA-D-MANNOSE'>MAN</scene>, <scene name='pdbligand=NAG:N-ACETYL-D-GLUCOSAMINE'>NAG</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=3vn4 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3vn4 OCA], [https://pdbe.org/3vn4 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=3vn4 RCSB], [https://www.ebi.ac.uk/pdbsum/3vn4 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=3vn4 ProSAT]</span></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=3vn4 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3vn4 OCA], [https://pdbe.org/3vn4 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=3vn4 RCSB], [https://www.ebi.ac.uk/pdbsum/3vn4 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=3vn4 ProSAT]</span></td></tr>
</table>
</table>
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== Function ==
== Function ==
[https://www.uniprot.org/uniprot/ATS13_HUMAN ATS13_HUMAN] Cleaves the vWF multimers in plasma into smaller forms.
[https://www.uniprot.org/uniprot/ATS13_HUMAN ATS13_HUMAN] Cleaves the vWF multimers in plasma into smaller forms.
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<div style="background-color:#fffaf0;">
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== Publication Abstract from PubMed ==
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BACKGROUND: An East Asian-specific P475S polymorphism in the gene encoding ADAMTS-13 causes an approximately 16% reduction in plasma ADAMTS-13 activity. OBJECTIVES: To demonstrate the impact of this dysfunctional polymorphism by characterizing the structure and activity of the P475S mutant protein. METHODS: We determined the crystal structure of the P475S mutant of ADAMTS-13-DTCS (DTCS-P475S, residues 287-685) and compared it with the wild-type structure. We determined the enzymatic parameters of ADAMTS-13-MDTCS (residues 75-685) and MDTCS-P475S, and further examined the effects of denaturants and reaction temperature on their activity. We also examined the cleavage of shear-treated von Willebrand factor (VWF) by MDTCS-P475S. RESULTS: MDTCS-P475S showed a reaction rate similar to that of wild-type MDTCS, but showed two-fold lower affinity for the peptidyl substrate, indicating that the Pro475-containing V-loop (residues 474-481) in the CA domain is a substrate-binding exosite. Structural analysis showed that the conformation of the V-loop was significantly different in DTCS-P475S and the wild type, where no obvious interactions of Ser475 with other residues were observed. This explains the higher susceptibility of the enzymatic activity of MDTCS-P475S to reaction environments such as denaturants and high temperature. MDTCS-P475S can moderately cleave shear-treated VWF. CONCLUSIONS: We have provided structural evidence that the P475S polymorphism in ADAMTS-13 leads to increased local structural instability, resulting in lowered affinity for the substrate without changing the reaction rate. The moderate activity of ADAMTS-13-P475S for shear-treated VWF is sufficient to prevent thrombotic thrombocytopenic purpura (TTP) onset.
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Crystal structure and enzymatic activity of an ADAMTS-13 mutant with the East Asian-specific P475S polymorphism.,Akiyama M, Nakayama D, Takeda S, Kokame K, Takagi J, Miyata T J Thromb Haemost. 2013 Jul;11(7):1399-406. doi: 10.1111/jth.12279. PMID:23621748<ref>PMID:23621748</ref>
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From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
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</div>
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<div class="pdbe-citations 3vn4" style="background-color:#fffaf0;"></div>
==See Also==
==See Also==

Current revision

Crystal structure of the exosite-containing fragment of human ADAMTS13 (P475S mutant)

PDB ID 3vn4

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Proteopedia Page Contributors and Editors (what is this?)

OCA

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