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Drug Discovery and Development: The Senna Plant and Phosphomevalonate Kinase Inhibition
Author(s) -
Brandl Corrine,
Hubbartt Katarena,
Herrmann Andrea,
Maala Nicole,
Meidl Alexandria,
Reznichek Hallie,
Kinscher Joseph,
Sem Daniel
Publication year - 2009
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.23.1_supplement.lb314
Subject(s) - enzyme , drug development , cholesterol , pharmacology , drug , biochemistry , biology , medicine
Heart disease is one of the most prominent causes of death in the United States. Hypercholesterolemia is an underlying factor leading to heart disease. By inhibiting the cholesterol synthesis pathway, scientists can develop ways to reduce the number of heart disease‐related deaths. One way could be by inhibiting the actions of phosphomevalonate kinase (PMK), a cytoplasmic enzyme found in the liver. The Valders SMART Team (Students Modeling A Research Topic), in collaboration with MSOE, built a 3D physical model of PMK using 3D printing technology. Both mevalonate 5‐phosphate (M5P) and ATP bind to the enzyme. Using ATP, PMK converts M5P to mevalonate 5‐diphosphate, a precursor to cholesterol. The inhibition of this process may be possible through a drug derived from the Indian senna plant, which is predicted to bind in place of M5P. Supported by a grant from NIH‐NCRR‐SEPA.