2 Å X‐ray structure of adamalysin II complexed with a peptide phosphonate inhibitor adopting a retro‐binding mode
1997; Wiley; Volume: 418; Issue: 3 Linguagem: Inglês
10.1016/s0014-5793(97)01401-4
ISSN1873-3468
AutoresMaurizio Cirilli, Carlo Gallina, E. Gavuzzo, Cesare Giordano, F. Xavier Gomis‐Rüth, B. Gorini, Lawrence F. Kress, F. Mazza, Mario Paglialunga Paradisi, G. Pochetti, V. Politi,
Tópico(s)Chemical Synthesis and Analysis
ResumoThe search of reprolysin inhibitors offers the possibility of intervention against both matrixins and ADAMs. Here we report the crystal structure of the complex between adamalysin II, a member of the reprolysin family, and a phosphonate inhibitor modeled on an endogenous venom tripeptide. The inhibitor occupies the primed region of the cleavage site adopting a retro-binding mode. The phosphonate group ligates the zinc ion in an asymmetric bidentate mode and the adjacent Trp indole system partly fills the primary specificity subsite S1'. An adamalysin-based model of tumor necrosis factor-alpha-converting enzyme (TACE) reveals a smaller S1' pocket for this enzyme.
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