2 angstrom X-ray structure of adamalysin II complexed with a peptide phosphonate inhibitor adopting a retro-binding mode

FEBS Letters
M CirilliV Politi

Abstract

The 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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Citations

May 12, 2004·Veterinary Immunology and Immunopathology·Joris J WijnkerJohanna Fink-Gremmels
Apr 12, 2000·Toxicon : Official Journal of the International Society on Toxinology·D H SouzaR C Garratt
Mar 7, 2001·European Journal of Medicinal Chemistry·S D'AlessioG Pochetti
Apr 28, 1999·Bioorganic & Medicinal Chemistry·S D'AlessioA Sella
Apr 13, 2001·Drug Discovery Today·M L. MossR C. Andrews
Jun 12, 2012·Acta Crystallographica. Section F, Structural Biology and Crystallization Communications·Troii HallMarc D Zack
Jul 23, 1999·Annals of the New York Academy of Sciences·C GallinaV Politi
Mar 7, 2014·Protein Science : a Publication of the Protein Society·Núria Cerdà-Costa, Francesc Xavier Gomis-Rüth
Jun 5, 2013·Toxicon : Official Journal of the International Society on Toxinology·Tsung-Lin ChouAndrew H-J Wang
Mar 6, 2012·Chemical Biology & Drug Design·Torsten LingottThomas Steinbrecher
Nov 10, 2007·The Journal of Biological Chemistry·Huey-Sheng ShiehAlfredo Tomasselli
Mar 10, 2005·Chemical Reviews·Joel D A TyndallDavid P Fairlie
Feb 24, 2005·European Journal of Medicinal Chemistry·Mariangela AgamennoneCarlo Gallina
Apr 10, 2010·Chemical Reviews·Praveen K MadalaDavid P Fairlie
Jun 15, 2005·Journal of Proteome Research·Claudia AndreiniAntonio Rosato
Oct 29, 2002·Inorganic Chemistry·Vladimir Pelmenschikov, Per E M Siegbahn

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