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PDBsum entry 2tcl
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Hydrolase (metalloprotease)
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PDB id
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2tcl
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References listed in PDB file
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Key reference
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Title
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Structure of the catalytic domain of human fibroblast collagenase complexed with an inhibitor.
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Authors
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N.Borkakoti,
F.K.Winkler,
D.H.Williams,
A.D'Arcy,
M.J.Broadhurst,
P.A.Brown,
W.H.Johnson,
E.J.Murray.
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Ref.
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Nat Struct Biol, 1994,
1,
106-110.
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PubMed id
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Abstract
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In rheumatoid and osteoarthritis, degradation of articular cartilage is mediated
by the matrix metalloproteinases collagenase, stromelysin and gelatinase. The
key event in this process is the cleavage of triple helical collagen by
collagenase. We have determined the crystal structure of the catalytic domain of
human recombinant fibroblast collagenase complexed with a synthetic inhibitor at
2.2 A resolution. The protein fold is similar to the amino termini of the zinc
endopeptidases astacin thermolysin and elastase despite a lack of primary
sequence homology. The conformation of the bound inhibitor provides a molecular
basis for the design of inhibitors of collagenase and other matrix
metalloproteinases. Such inhibitors should be useful in the treatment of a
variety of diseases including arthritis and cancer.
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