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PDBsum entry 1kbc
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Metalloproteinase
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PDB id
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1kbc
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Contents |
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* Residue conservation analysis
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Enzyme class:
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E.C.3.4.24.34
- neutrophil collagenase.
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Reaction:
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Cleavage of interstitial collagens in the triple helical domain. Unlike EC 3.4.24.7, this enzyme cleaves type III collagen more slowly than type I.
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Cofactor:
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Ca(2+); Zn(2+)
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Eur J Biochem
247:356-363
(1997)
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PubMed id:
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1.8-A crystal structure of the catalytic domain of human neutrophil collagenase (matrix metalloproteinase-8) complexed with a peptidomimetic hydroxamate primed-side inhibitor with a distinct selectivity profile.
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M.Betz,
P.Huxley,
S.J.Davies,
Y.Mushtaq,
M.Pieper,
H.Tschesche,
W.Bode,
F.X.Gomis-Rüth.
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ABSTRACT
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Matrix metalloproteinases (MMP) are zinc endopeptidases involved in tissue
remodelling. They have been implicated in a series of pathologies, including
cancer, arthritis, joint destruction and Alzheimer's disease. Human neutrophil
collagenase represents one of the three interstitial collagenases that cleave
triple-helical collagen of type I, II and III. Its catalytic domain (residues
Phe79-Gly242) has been heterologously expressed in Escherichia coli and
crystallized as a non-covalent complex with the hydroxamate inhibitor BB-1909,
which has distinct selectivity against different MMP, in a crystal form. The
crystal structure, refined to 0.18-nm resolution, shows that BB-1909 is a
right-hand-side inhibitor that binds to the S1'-S3' subsites and coordinates to
the catalytic Zn2+ in a bidentate manner via the hydroxyl and carbonyl oxygen
atoms of the hydroxamate group in a similar manner to batimastat. The
collagenase/BB-1909 complex is described in detail and compared with the
collagenase/batimastat complex. These studies provide information on MMP
specificity and thus may assist the development of more-selective MMP inhibitors.
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Literature references that cite this PDB file's key reference
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PubMed id
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Reference
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C.Gialeli,
A.D.Theocharis,
and
N.K.Karamanos
(2011).
Roles of matrix metalloproteinases in cancer progression and their pharmacological targeting.
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FEBS J,
278,
16-27.
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N.Cerdà-Costa,
T.Guevara,
A.Y.Karim,
M.Ksiazek,
K.A.Nguyen,
J.L.Arolas,
J.Potempa,
and
F.X.Gomis-Rüth
(2011).
The structure of the catalytic domain of Tannerella forsythia karilysin reveals it is a bacterial xenologue of animal matrix metalloproteinases.
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Mol Microbiol,
79,
119-132.
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PDB codes:
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R.Roy,
J.Yang,
and
M.A.Moses
(2009).
Matrix metalloproteinases as novel biomarkers and potential therapeutic targets in human cancer.
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J Clin Oncol,
27,
5287-5297.
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S.Higashi,
and
K.Miyazaki
(2008).
Identification of amino acid residues of the matrix metalloproteinase-2 essential for its selective inhibition by beta-amyloid precursor protein-derived inhibitor.
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J Biol Chem,
283,
10068-10078.
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K.Yamamoto,
S.Higashi,
M.Kioi,
J.Tsunezumi,
K.Honke,
and
K.Miyazaki
(2006).
Binding of active matrilysin to cell surface cholesterol sulfate is essential for its membrane-associated proteolytic action and induction of homotypic cell adhesion.
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J Biol Chem,
281,
9170-9180.
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H.B.Newton
(2004).
Molecular neuro-oncology and the development of targeted therapeutic strategies for brain tumors. Part 3: brain tumor invasiveness.
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Expert Rev Anticancer Ther,
4,
803-821.
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N.Ramnath,
and
P.J.Creaven
(2004).
Matrix metalloproteinase inhibitors.
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Curr Oncol Rep,
6,
96.
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S.Higashi,
and
K.Miyazaki
(2003).
Identification of a region of beta-amyloid precursor protein essential for its gelatinase A inhibitory activity.
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J Biol Chem,
278,
14020-14028.
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M.Hidalgo,
and
S.G.Eckhardt
(2001).
Development of matrix metalloproteinase inhibitors in cancer therapy.
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J Natl Cancer Inst,
93,
178-193.
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A.Ovens,
J.A.Joule,
and
K.E.Kadler
(2000).
Design and synthesis of acidic dipeptide hydroxamate inhibitors of procollagen C-proteinase.
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J Pept Sci,
6,
489-495.
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I.Broutin-L'Hermite,
M.Ries-Kautt,
and
A.Ducruix
(2000).
1.7 A x-ray structure of space-grown collagenase crystals.
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Acta Crystallogr D Biol Crystallogr,
56,
376-378.
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P.D.Brown
(2000).
Ongoing trials with matrix metalloproteinase inhibitors.
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Expert Opin Investig Drugs,
9,
2167-2177.
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D.E.Brodersen,
J.Nyborg,
and
M.Kjeldgaard
(1999).
Zinc-binding site of an S100 protein revealed. Two crystal structures of Ca2+-bound human psoriasin (S100A7) in the Zn2+-loaded and Zn2+-free states.
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Biochemistry,
38,
1695-1704.
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PDB codes:
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F.J.Moy,
P.K.Chanda,
J.M.Chen,
S.Cosmi,
W.Edris,
J.S.Skotnicki,
J.Wilhelm,
and
R.Powers
(1999).
NMR solution structure of the catalytic fragment of human fibroblast collagenase complexed with a sulfonamide derivative of a hydroxamic acid compound.
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Biochemistry,
38,
7085-7096.
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PDB codes:
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L.L.Johnson,
D.A.Bornemeier,
J.A.Janowicz,
J.Chen,
A.G.Pavlovsky,
and
D.F.Ortwine
(1999).
Effect of species differences on stromelysin-1 (MMP-3) inhibitor potency. An explanation of inhibitor selectivity using homology modeling and chimeric proteins.
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J Biol Chem,
274,
24881-24887.
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The most recent references are shown first.
Citation data come partly from CiteXplore and partly
from an automated harvesting procedure. Note that this is likely to be
only a partial list as not all journals are covered by
either method. However, we are continually building up the citation data
so more and more references will be included with time.
Where a reference describes a PDB structure, the PDB
codes are
shown on the right.
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Links
