3HY9

Crystal Structure of the Catalytic Domain of ADAMTS-5 in Complex with an Amino-2-indanol compound

Summary for 3HY9

• Entry DOI: 10.2210/pdb3hy9/pdb
• Related: 3B8Z 3HY7 3HYG
• Descriptor: Catalytic Domain of ADAMTS-5, ZINC ION, CALCIUM ION, ... (5 entities in total)
• Functional Keywords: alpha/beta structure, central five stranded beta-sheet, hydrolase
• Biological source: Homo sapiens
• Cellular location: Secreted, extracellular space, extracellular matrix : Q9UNA0
• Total number of polymer chains: 2
• Total formula weight: 50123.58

Authors

Shieh, H.-S.,Williams, J.M.,Caspers, N.,Mathis, K.J.,Tortorella, M.D.,Tomasselli, A. (deposition date: 2009-06-22, release date: 2009-07-07, Last modification date: 2024-10-30)

Primary citation

Tortorella, M.D.,Tomasselli, A.G.,Mathis, K.J.,Schnute, M.E.,Woodard, S.S.,Munie, G.,Williams, J.M.,Caspers, N.,Wittwer, A.J.,Malfait, A.M.,Shieh, H.S.
Structural and inhibition analysis reveals the mechanism of selectivity of a series of aggrecanase inhibitors
J.Biol.Chem., 284:24185-24191, 2009

PubMed Abstract: Several inhibitors of a series of cis-1(S)2(R)-amino-2-indanol-based compounds were reported to be selective for the aggrecanases, ADAMTS-4 and -5 over other metalloproteases. To understand the nature of this selectivity for aggrecanases, the inhibitors, along with the broad spectrum metalloprotease inhibitor marimastat, were independently bound to the catalytic domain of ADAMTS-5, and the corresponding crystal structures were determined. By comparing the structures, it was determined that the specificity of the relative inhibitors for ADAMTS-5 was not driven by a specific interaction, such as zinc chelation, hydrogen bonding, or charge interactions, but rather by subtle and indirect factors, such as water bridging, ring rigidity, pocket size, and shape, as well as protein conformation flexibility.

PubMed: 19586907
DOI: 10.1074/jbc.M109.029116

Experimental method

X-RAY DIFFRACTION (2.02 Å)