B.Sekula
and
A.Bujacz
(2016).
Structural Insights into the Competitive Binding of Diclofenac and Naproxen by Equine Serum Albumin.
J Med Chem,
59,
82-89.
PubMed id: 26652101
DOI: 10.1021/acs.jmedchem.5b00909
Structural Insights into the Competitive Binding of Diclofenac and Naproxen by Equine Serum Albumin.
B.Sekula,
A.Bujacz.
ABSTRACT
The binding modes to equine serum albumin (ESA) of two nonsteroidal
anti-inflammatory drugs (NSAIDs), diclofenac (Dic) and naproxen (Nps), were
studied by X-ray crystallography and isothermal titration calorimetry. On the
basis of the crystal structure of ESA/Dic determined to a resolution of 1.92 Å
and the structure of the previously described ESA/Nps complex (2.42 Å), it was
found that both NSAIDs bind within drug site 2 (DS2) of ESA and both occupy
secondary binding sites in separate cavities of domain II (Nps) and domain III
(Dic). The two structures of the ternary complex ESA/Dic/Nps, obtained by
competitive cocrystallization (2.19 Å) and through a displacement experiment
(2.35 Å), were determined to investigate possible competition of these widely
used pharmaceutical drugs in binding to ESA. In these complexes Nps occupies the
DS2 pocket common for both drugs, whereas the other distinct binding sites of
Dic and Nps remain unaffected. These results suggest that combined application
of both drugs may result in increased concentration of free diclofenac in plasma.
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