2 angstrom X-ray structure of adamalysin II complexed with a peptide phosphonate inhibitor adopting a retro-binding mode.
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.
Cirilli
M
M
Ist. Strutturistica Chimica, CNR, Rome, Italy.
Gallina
C
C
Gavuzzo
E
E
Giordano
C
C
Gomis-Rüth
F X
FX
Gorini
B
B
Kress
L F
LF
Mazza
F
F
Paradisi
M P
MP
Pochetti
G
G
Politi
V
V
D003435:Crotalid Venoms / Q000378:metabolism; D018360:Crystallography, X-Ray; D004791:Enzyme Inhibitors / Q000737:chemistry*; D008666:Metalloendopeptidases / Q000737:chemistry* / Q000378:metabolism; D009943:Organophosphorus Compounds / Q000737:chemistry*; D010455:Peptides / Q000737:chemistry; D011485:Protein Binding; D011487:Protein Conformation
D003435:Crotalid Venoms; D004791:Enzyme Inhibitors; D009943:Organophosphorus Compounds; D010455:Peptides; D008666:Metalloendopeptidases; C028220:Crotalus adamanteus proteinase II