3EWJ

Crystal structure of catalytic domain of TACE with carboxylate inhibitor

Summary for 3EWJ

• Entry DOI: 10.2210/pdb3ewj/pdb
• Related: 1bkc 2fv9 3e8r
• Related PRD ID: PRD_000919
• Descriptor: ADAM 17, ZINC ION, N-{(2R)-2-[2-(hydroxyamino)-2-oxoethyl]-4-methylpentanoyl}-3-methyl-L-valyl-N-(2-aminoethyl)-L-alaninamide, ... (5 entities in total)
• Functional Keywords: tace, adam17, hydrolase, cleavage on pair of basic residues, glycoprotein, membrane, metal-binding, metalloprotease, notch signaling pathway, phosphoprotein, protease, sh3-binding, transmembrane, zymogen
• Biological source: Homo sapiens (Human)
• Cellular location: Membrane; Single-pass type I membrane protein: P78536
• Total number of polymer chains: 2
• Total formula weight: 62347.39

Authors

Orth, P. (deposition date: 2008-10-15, release date: 2008-11-18, Last modification date: 2024-11-06)

Primary citation

Guo, Z.,Orth, P.,Wong, S.C.,Lavey, B.J.,Shih, N.Y.,Niu, X.,Lundell, D.J.,Madison, V.,Kozlowski, J.A.
Discovery of novel spirocyclopropyl hydroxamate and carboxylate compounds as TACE inhibitors.
Bioorg.Med.Chem.Lett., 19:54-57, 2009

PubMed Abstract: We have discovered nanomolar inhibitors of TNF-alpha convertase (TACE) comprised of a novel spirocyclic scaffold and either a carboxylate or hydroxamate zinc binding moiety. X-ray crystal structures and computer models of selected compounds binding to TACE explain the observed SAR. We report the first TACE X-ray crystal structure for an inhibitor with a carboxylate zinc ligand.

PubMed: 19054672
DOI: 10.1016/j.bmcl.2008.11.034

Experimental method

X-RAY DIFFRACTION (1.8 Å)