Abstract:
:The conformation of the sodium salt of mycophenolic acid (MPA), a potent inhibitor of inosine monophosphate dehydrogenase (IMPD), derived from 1D DIFNOE and 2D ROESY experiments in water and molecular dynamics (MD) is described. The hexenoic acid side chain conformation consistent with the NMR data was similar to that seen in the X-ray structure of MPA. The solution conformation was applied in a molecular modeling study in order to explore the potential features of enzyme binding. Our results, based on striking similarities in molecular volume and electrostatic isopotential between MPA and cofactor NAD+, lead to the suggestion that MPA is capable of binding to the nicotinamide site of IMPD and mimicking the NAD+ inverse regulation of the enzyme. In addition, our proposed model is in good agreement with the observed high affinity of the dinucleotide analogues thiazole- and selenazole-4-carboxamide adenine dinucleotide to IMPD.
journal_name
J Med Chemjournal_title
Journal of medicinal chemistryauthors
Makara GM,Keserû GM,Kajtár-Peredy M,Anderson WKdoi
10.1021/jm950600msubject
Has Abstractpub_date
1996-03-15 00:00:00pages
1236-42issue
6eissn
0022-2623issn
1520-4804pii
jm950600mjournal_volume
39pub_type
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