3AIG: ADAMALYSIN II WITH PEPTIDOMIMETIC INHIBITOR POL656

Citation:
Abstract
Crotalus adamanteus snake venom adamalysin II is the structural prototype of the adamalysin or ADAM family comprising proteolytic domains of snake venom metalloproteinases, multimodular mammalian reproductive tract proteins, and tumor necrosis factor alpha convertase, TACE, involved in the release of the inflammatory cytokine, TNFalpha. The structure of adamalysin II in noncovalent complex with two small-molecule right-hand side peptidomimetic inhibitors (Pol 647 and Pol 656) has been solved using X-ray diffraction data up to 2.6 and 2.8 A resolution. The inhibitors bind to the S'-side of the proteinase, inserting between two protein segments, establishing a mixed parallel-antiparallel three-stranded beta-sheet and coordinate the central zinc ion in a bidentate manner via their two C-terminal oxygen atoms. The proteinase-inhibitor complexes are described in detail and are compared with other known structures. An adamalysin-based model of the active site of TACE reveals that these small molecules would probably fit into the active site cleft of this latter metalloproteinase, providing a starting model for the rational design of TACE inhibitors.
PDB ID: 3AIGDownload
MMDB ID: 58269
PDB Deposition Date: 1997/10/12
Updated in MMDB: 2012/10
Experimental Method:
x-ray diffraction
Resolution: 2.8  Å
Source Organism:
Similar Structures:
Biological Unit for 3AIG: dimeric; determined by author
Molecular Components in 3AIG
Label Count Molecule
Proteins (2 molecules)
2
Adamalysin II
Molecule annotation
Chemicals (8 molecules)
1
2
2
2
3
2
4
2
* Click molecule labels to explore molecular sequence information.

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