3G42

Crystal Structure of TACE with Tryptophan Sulfonamide Derivative Inhibitor

Summary for 3G42

• Entry DOI: 10.2210/pdb3g42/pdb
• Related: 1BKC 1ZXC 2A8H 2I47
• Descriptor: ADAM 17, N-{[4-(but-2-yn-1-yloxy)phenyl]sulfonyl}-5-methyl-D-tryptophan, ZINC ION, ... (4 entities in total)
• Functional Keywords: tace/adam-17, tace-inhibitor complex, zn-endopeptidase, alternative splicing, cleavage on pair of basic residues, glycoprotein, hydrolase, membrane, metal-binding, metalloprotease, notch signaling pathway, phosphoprotein, polymorphism, protease, sh3-binding, transmembrane, zinc, zymogen
• Biological source: Homo sapiens (human)
• Cellular location: Membrane; Single-pass type I membrane protein: P78536
• Total number of polymer chains: 4
• Total formula weight: 132321.05

Authors

Xu, W.,Park, K.,Gopalsamy, A.,Aplasca, A.,Zhang, Y.H.,Levin, J.I. (deposition date: 2009-02-03, release date: 2009-05-19, Last modification date: 2024-10-09)

Primary citation

Park, K.,Gopalsamy, A.,Aplasca, A.,Ellingboe, J.W.,Xu, W.,Zhang, Y.,Levin, J.I.
Synthesis and activity of tryptophan sulfonamide derivatives as novel non-hydroxamate TNF-alpha converting enzyme (TACE) inhibitors.
Bioorg.Med.Chem., 17:3857-3865, 2009

PubMed Abstract: A novel series of non-hydroxamate tryptophan sulfonamide derivatives containing a butynyloxy P1' moiety was identified as inhibitors of TNF-alpha converting enzyme (TACE). The structure-activity relationship of the series was examined via substitution on the tryptophan indole ring. Of the compounds investigated, 2-(4-(but-2-ynyloxy)phenylsulfonamido)-3-(1-(4-methoxybenzyl)-1H-indol-3-yl)propanoic acid (12p) has the best in vitro potency against isolated TACE enzyme with an IC(50) of 80 nM. Compound 12p also shows good selectivity over MMP-1, -13, -14.

PubMed: 19410464
DOI: 10.1016/j.bmc.2009.04.033

Experimental method

X-RAY DIFFRACTION (2.1 Å)