3L0V

Crystal structure of catalytic domain of TACE with the first hydantoin inhibitor occupying the S1' pocket

Summary for 3L0V

• Entry DOI: 10.2210/pdb3l0v/pdb
• Related: 1bkc 3KMC 3L0T 3LE9 3LEA
• Descriptor: Disintegrin and metalloproteinase domain-containing protein 17, ZINC ION, (5R)-5-[(5-methoxy-3-oxo-1,3-dihydro-2H-indazol-2-yl)methyl]-5-methylimidazolidine-2,4-dione, ... (4 entities in total)
• Functional Keywords: metal-binding, metalloprotease, notch signaling pathway, protease, hydrolase-hydrolase inhibitor complex, hydrolase/hydrolase inhibitor
• Biological source: Homo sapiens (human)
• Cellular location: Membrane; Single-pass type I membrane protein: P78536
• Total number of polymer chains: 2
• Total formula weight: 61849.64

Authors

Orth, P. (deposition date: 2009-12-10, release date: 2010-03-02, Last modification date: 2024-11-20)

Primary citation

Yu, W.,Guo, Z.,Orth, P.,Madison, V.,Chen, L.,Dai, C.,Feltz, R.J.,Girijavallabhan, V.M.,Kim, S.H.,Kozlowski, J.A.,Lavey, B.J.,Li, D.,Lundell, D.,Niu, X.,Piwinski, J.J.,Popovici-Muller, J.,Rizvi, R.,Rosner, K.E.,Shankar, B.B.,Shih, N.Y.,Siddiqui, M.A.,Sun, J.,Tong, L.,Umland, S.,Wong, M.K.,Yang, D.Y.,Zhou, G.
Discovery and SAR of hydantoin TACE inhibitors.
Bioorg.Med.Chem.Lett., 20:1877-1880, 2010

PubMed Abstract: We disclose inhibitors of TNF-alpha converting enzyme (TACE) designed around a hydantoin zinc binding moiety. Crystal structures of inhibitors bound to TACE revealed monodentate coordination of the hydantoin to the zinc. SAR, X-ray, and modeling designs are described. To our knowledge, these are the first reported X-ray structures of TACE with a hydantoin zinc ligand.

PubMed: 20172725
DOI: 10.1016/j.bmcl.2010.01.148

Experimental method

X-RAY DIFFRACTION (1.75 Å)