2AIG

ADAMALYSIN II WITH PEPTIDOMIMETIC INHIBITOR POL647

Summary for 2AIG

• Entry DOI: 10.2210/pdb2aig/pdb
• Related PRD ID: PRD_000297
• Descriptor: ADAMALYSIN II, N-(furan-2-ylcarbonyl)-L-leucyl-L-tryptophan, ZINC ION, ... (6 entities in total)
• Functional Keywords: zinc protease, metalloendopetidase, complex of metalloprotease-inhibitor, hydrolast-hydrolase inhibitor complex, hydrolast/hydrolase inhibitor
• Biological source: Crotalus adamanteus (eastern diamondback rattlesnake)
• Total number of polymer chains: 1
• Total formula weight: 23792.40

Authors

Gomis-Rueth, F.X.,Meyer, E.F.,Kress, L.F.,Politi, V. (deposition date: 1997-10-12, release date: 1998-04-15, Last modification date: 2024-10-23)

Primary citation

Gomis-Ruth, F.X.,Meyer, E.F.,Kress, L.F.,Politi, V.
Structures of adamalysin II with peptidic inhibitors. Implications for the design of tumor necrosis factor alpha convertase inhibitors.
Protein Sci., 7:283-292, 1998

PubMed 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.

PubMed: 9521103

Experimental method

X-RAY DIFFRACTION (2.6 Å)