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PDBsum entry 2rjp
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References listed in PDB file
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Key reference
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Title
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Crystal structures of the two major aggrecan degrading enzymes, Adamts4 and adamts5.
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Authors
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L.Mosyak,
K.Georgiadis,
T.Shane,
K.Svenson,
T.Hebert,
T.Mcdonagh,
S.Mackie,
S.Olland,
L.Lin,
X.Zhong,
R.Kriz,
E.L.Reifenberg,
L.A.Collins-Racie,
C.Corcoran,
B.Freeman,
R.Zollner,
T.Marvell,
M.Vera,
P.E.Sum,
E.R.Lavallie,
M.Stahl,
W.Somers.
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Ref.
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Protein Sci, 2008,
17,
16-21.
[DOI no: ]
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PubMed id
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Abstract
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Aggrecanases are now believed to be the principal proteinases responsible for
aggrecan degradation in osteoarthritis. Given their potential as a drug target,
we solved crystal structures of the two most active human aggrecanase isoforms,
ADAMTS4 and ADAMTS5, each in complex with bound inhibitor and one wherein the
enzyme is in apo form. These structures show that the unliganded and
inhibitor-bound enzymes exhibit two essentially different catalytic-site
configurations: an autoinhibited, nonbinding, closed form and an open, binding
form. On this basis, we propose that mature aggrecanases exist as an ensemble of
at least two isomers, only one of which is proteolytically active.
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Figure 2.
Figure 2. Molecular surfaces of the active sites with inhibitor bound and detailed view of the interactions involved. (A) Stereo surface
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The above figure is
reprinted
by permission from the Protein Society:
Protein Sci
(2008,
17,
16-21)
copyright 2008.
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