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* Residue conservation analysis
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PDB id:
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Hydrolase
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Title:
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Crystal structure of mmp3 complexed with a heterocycle- based inhibitor
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Structure:
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Stromelysin-1 precursor. Chain: a, b. Fragment: catalytic domain. Synonym: mmp-3. Engineered: yes
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Source:
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Homo sapiens. Human. Organism_taxid: 9606. Cell: fibroblast. Expressed in: escherichia coli. Expression_system_taxid: 562
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Resolution:
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2.44Å
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R-factor:
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0.277
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R-free:
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0.315
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Authors:
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S.Pikul,K.M.Dunham,N.G.Almstead,B.De,M.G.Natchus,Y.O.Taiwo, L.E.Williams,B.A.Hynd,L.C.Hsieh,M.J.Janusz,F.Gu,G.E.Mieling
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Key ref:
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S.Pikul
et al.
(2001).
Heterocycle-based MMP inhibitors with P2' substituents.
Bioorg Med Chem Lett,
11,
1009-1013.
PubMed id:
DOI:
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Date:
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25-Oct-99
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Release date:
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25-Oct-00
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PROCHECK
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Headers
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References
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P08254
(MMP3_HUMAN) -
Stromelysin-1
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Seq:
Struc:
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477 a.a.
169 a.a.
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Key: |
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PfamA domain |
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Secondary structure |
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CATH domain |
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Enzyme class:
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E.C.3.4.24.17
- Stromelysin 1.
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Reaction:
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Preferential cleavage where P1', P2' and P3' are hydrophobic residues.
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Cofactor:
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Calcium; Zinc
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Gene Ontology (GO) functional annotation
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Cellular component
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extracellular matrix
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1 term
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Biological process
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proteolysis
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1 term
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Biochemical function
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metallopeptidase activity
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3 terms
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DOI no:
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Bioorg Med Chem Lett
11:1009-1013
(2001)
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PubMed id:
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Heterocycle-based MMP inhibitors with P2' substituents.
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S.Pikul,
K.M.Dunham,
N.G.Almstead,
B.De,
M.G.Natchus,
Y.O.Taiwo,
L.E.Williams,
B.A.Hynd,
L.C.Hsieh,
M.J.Janusz,
F.Gu,
G.E.Mieling.
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ABSTRACT
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Potent and selective inhibition of matrix metalloproteinases was demonstrated
for a series of sulfonamide-based hydroxamic acids. The design of the
heterocyclic sulfonamides incorporates a six- or seven-member central ring with
a P2' substituent that can be modified. Binding interactions of this substituent
at the S2' site are believed to contribute to high inhibitory potency against
stromelysin, collagenase-3 and gelatinases A and B, and to provide selectivity
against collagenase-1 and matrilysin. An X-ray structure of a stromelysin
inhibitor complex was obtained to provide insights into the SAR and selectivity
trends observed for the series.
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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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L.A.Alcaraz,
L.Banci,
I.Bertini,
F.Cantini,
A.Donaire,
and
L.Gonnelli
(2007).
Matrix metalloproteinase-inhibitor interaction: the solution structure of the catalytic domain of human matrix metalloproteinase-3 with different inhibitors.
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J Biol Inorg Chem, 12,
1197-1206.
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PDB codes:
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C.T.Supuran,
A.Casini,
and
A.Scozzafava
(2003).
Protease inhibitors of the sulfonamide type: anticancer, antiinflammatory, and antiviral agents.
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Med Res Rev, 23,
535-558.
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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
