3B2Z

Crystal Structure of ADAMTS4 (apo form)

Summary for 3B2Z

• Entry DOI: 10.2210/pdb3b2z/pdb
• Descriptor: ADAMTS-4, ZINC ION, CALCIUM ION, ... (4 entities in total)
• Functional Keywords: metalloprotease, aggrecanase, cleavage on pair of basic residues, extracellular matrix, glycoprotein, hydrolase, metal-binding, secreted, zymogen
• Biological source: Homo sapiens (human)
• Cellular location: Secreted, extracellular space, extracellular matrix (By similarity): O75173
• Total number of polymer chains: 8
• Total formula weight: 274937.80

Authors

Mosyak, L.,Stahl, M.,Somers, W. (deposition date: 2007-10-19, release date: 2007-12-25, Last modification date: 2024-11-06)

Primary citation

Mosyak, L.,Georgiadis, K.,Shane, T.,Svenson, K.,Hebert, T.,McDonagh, T.,Mackie, S.,Olland, S.,Lin, L.,Zhong, X.,Kriz, R.,Reifenberg, E.L.,Collins-Racie, L.A.,Corcoran, C.,Freeman, B.,Zollner, R.,Marvell, T.,Vera, M.,Sum, P.E.,Lavallie, E.R.,Stahl, M.,Somers, W.
Crystal structures of the two major aggrecan degrading enzymes, ADAMTS4 and ADAMTS5.
Protein Sci., 17:16-21, 2008

PubMed Abstract: Aggrecanases are now believed to be the principal proteinases responsible for aggrecan degradation in osteoarthritis. Given their potential as a drug target, we solved crystal structures of the two most active human aggrecanase isoforms, ADAMTS4 and ADAMTS5, each in complex with bound inhibitor and one wherein the enzyme is in apo form. These structures show that the unliganded and inhibitor-bound enzymes exhibit two essentially different catalytic-site configurations: an autoinhibited, nonbinding, closed form and an open, binding form. On this basis, we propose that mature aggrecanases exist as an ensemble of at least two isomers, only one of which is proteolytically active.

PubMed: 18042673
DOI: 10.1110/ps.073287008

Experimental method

X-RAY DIFFRACTION (2.8 Å)