View source for 9rwm


==Crystal structure of human ADAMTS-5 Cb and Spacer domains==
<StructureSection load='9rwm' size='340' side='right'caption='[[9rwm]], [[Resolution|resolution]] 2.60&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[9rwm]] is a 3 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=9RWM OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=9RWM 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]] 2.6&#8491;</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=9rwm FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=9rwm OCA], [https://pdbe.org/9rwm PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=9rwm RCSB], [https://www.ebi.ac.uk/pdbsum/9rwm PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=9rwm ProSAT]</span></td></tr>
</table>
== Function ==
[https://www.uniprot.org/uniprot/ATS5_HUMAN ATS5_HUMAN] Cleaves aggrecan, a cartilage proteoglycan, and may be involved in its turnover. May play an important role in the destruction of aggrecan in arthritic diseases. May play a role in proteolytic processing mostly during the peri-implantation period.
<div style="background-color:#fffaf0;">
== Publication Abstract from PubMed ==
The ADAMTS (a disintegrin-like and metalloproteinase domain with thrombospondin type 1 motifs) family of secreted metalloproteinases plays essential roles in extracellular matrix remodeling. ADAMTS-5 contributes to cartilage degradation, cleaving proteoglycans such as aggrecan and versican, and being involved in both physiological tissue turnover and pathological processes such as osteoarthritis and atherosclerosis. Although structural insights into its catalytic domain have informed inhibitor development, the role of ancillary domains, particularly the spacer domain, in substrate recognition and specificity remains underexplored. Here, we report the crystal structure of a segment of human ADAMTS-5 encompassing the C-terminal portion of the cysteine-rich domain and the spacer domain (residues 694-876). This structure reveals critical features of the spacer domain, including the hypervariable loops that function as exosites essential for the binding of aggrecan and versican. Our findings provide new structural insights into the molecular determinants of the substrate specificity of ADAMTS-5 and underscore the spacer domain as a promising target for the development of selective inhibitors.

Structure, substrate recognition and therapeutic targeting of the human ADAMTS-5 spacer domain.,Milani M, Visintin M, Krastanova I, Visentini M, Margotti E, Ugolini G, Bolognesi M, Rovati LC, Mastrangelo E Acta Crystallogr D Struct Biol. 2026 Jan 1;82(Pt 1):53-61. doi: , 10.1107/S2059798325010290. Epub 2026 Jan 1. PMID:41334750<ref>PMID:41334750</ref>

From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
</div>
<div class="pdbe-citations 9rwm" style="background-color:#fffaf0;"></div>
== References ==
<references/>
__TOC__
</StructureSection>
[[Category: Homo sapiens]]
[[Category: Large Structures]]
[[Category: Mastrangelo E]]
[[Category: Milani M]]