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PDBsum entry 2aig
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Hydrolast/hydrolase inhibitor
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PDB id
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2aig
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Contents |
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* Residue conservation analysis
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References listed in PDB file
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Key reference
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Title
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Structures of adamalysin ii with peptidic inhibitors. Implications for the design of tumor necrosis factor alpha convertase inhibitors.
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Authors
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F.X.Gomis-Rüth,
E.F.Meyer,
L.F.Kress,
V.Politi.
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Ref.
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Protein Sci, 1998,
7,
283-292.
[DOI no: ]
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PubMed id
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Abstract
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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.
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Secondary reference #1
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Title
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Refined 2.0 a X-Ray crystal structure of the snake venom zinc-Endopeptidase adamalysin ii. Primary and tertiary structure determination, Refinement, Molecular structure and comparison with astacin, Collagenase and thermolysin.
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Authors
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F.X.Gomis-Rüth,
L.F.Kress,
J.Kellermann,
I.Mayr,
X.Lee,
R.Huber,
W.Bode.
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Ref.
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J Mol Biol, 1994,
239,
513-544.
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PubMed id
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Secondary reference #2
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Title
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First structure of a snake venom metalloproteinase: a prototype for matrix metalloproteinases/collagenases.
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Authors
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F.X.Gomis-Rüth,
L.F.Kress,
W.Bode.
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Ref.
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Embo J, 1993,
12,
4151-4157.
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PubMed id
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