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PDBsum entry 4z0l
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Oxidoreductase/oxidoreductase inhibitor
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PDB id
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4z0l
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PDB id:
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| Name: |
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Oxidoreductase/oxidoreductase inhibitor
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Title:
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The murine cyclooxygenase-2 complexed with a nido-dicarbaborate- containing indomethacin derivative
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Structure:
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Prostaglandin g/h synthase 2. Chain: a, b, c, d. Fragment: unp residues 18-604. Synonym: cyclooxygenase-2,cox-2,glucocorticoid-regulated inflammatory cyclooxygenase,gripghs,macrophage activation-associated marker protein p71/73,pes-2,phs ii,prostaglandin h2 synthase 2,pghs-2, prostaglandin-endoperoxide synthase 2,tis10 protein. Engineered: yes
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Source:
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Mus musculus. Mouse. Organism_taxid: 10090. Gene: ptgs2, cox-2, cox2, pghs-b, tis10. Expressed in: spodoptera frugiperda. Expression_system_taxid: 7108. Expression_system_cell_line: sf21.
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Resolution:
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2.29Å
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R-factor:
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0.212
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R-free:
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0.250
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Authors:
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S.Xu,W.Neumann,S.Banerjee,E.Hey-Hawkins,L.J.Marnett
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Key ref:
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W.Neumann
et al.
(2016).
nido-Dicarbaborate Induces Potent and Selective Inhibition of Cyclooxygenase-2.
Chemmedchem,
11,
175-178.
PubMed id:
DOI:
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Date:
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26-Mar-15
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Release date:
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10-Jun-15
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PROCHECK
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Headers
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References
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Q05769
(PGH2_MOUSE) -
Prostaglandin G/H synthase 2 from Mus musculus
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Seq:
Struc:
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604 a.a.
551 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.1.14.99.1
- prostaglandin-endoperoxide synthase.
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Reaction:
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(5Z,8Z,11Z,14Z)-eicosatetraenoate + AH2 + 2 O2 = prostaglandin H2 + A + H2O
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(5Z,8Z,11Z,14Z)-eicosatetraenoate
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+
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AH2
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+
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2
×
O2
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=
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prostaglandin H2
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+
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+
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H2O
Bound ligand (Het Group name = )
matches with 51.11% similarity
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Molecule diagrams generated from .mol files obtained from the
KEGG ftp site
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DOI no:
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Chemmedchem
11:175-178
(2016)
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PubMed id:
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nido-Dicarbaborate Induces Potent and Selective Inhibition of Cyclooxygenase-2.
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W.Neumann,
S.Xu,
M.B.Sárosi,
M.S.Scholz,
B.C.Crews,
K.Ghebreselasie,
S.Banerjee,
L.J.Marnett,
E.Hey-Hawkins.
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ABSTRACT
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Carbaboranes are increasingly studied as pharmacophores, particularly as
replacements for aromatic systems. However, especially ortho-carbaborane is
prone to degradation of the cluster, which hampers biological application. This
study demonstrates that deboronation of the cluster may not only lead to a more
active analogue, but can also improve the solubility and stability of a
carbaborane-containing inhibitor. Notably, introduction of a nido-dicarbaborate
cluster into the cyclooxygenase (COX) inhibitor indomethacin results in
remarkably increased inhibitory potency and selectivity for COX-2 relative to
the respective phenyl analogue. The first crystal structure of a
carbaborane-containing inhibitor bound to COX-2 further reveals a novel binding
mode for the inhibitor that is strikingly different from that of indomethacin.
These results indicate that nido-dicarbaborate is a promising pharmacophore that
exhibits properties which are also highly beneficial for its introduction into
other inhibitor classes.
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