Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: EC:6.2.1.1 (ACS)
 78,556 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Protein prenylation is a ubiquitous covalent post-translational modification found in all eukaryotic cells, comprising attachment of either a farnesyl or a geranylgeranyl isoprenoid. It is essential for the proper cellular activity of numerous proteins, including Ras family GTPases and heterotrimeric G-proteins. Inhibition of prenylation has been extensively investigated to suppress the activity of oncogenic Ras proteins to achieve antitumor activity. Here, we review the biochemistry of the prenyltransferase enzymes and numerous isoprenoid analogs synthesized to investigate various aspects of prenylation and prenyltransferases. We also give an account of the current status of prenyltransferase inhibitors as potential therapeutics against several diseases including cancers, progeria, aging, parasitic diseases, and bacterial and viral infections. Finally, we discuss recent progress in utilizing protein prenylation for site-specific protein labeling for various biotechnology applications.
ACS Chem Biol 2015 Jan 16
PMID:Protein prenylation: enzymes, therapeutics, and biotechnology applications. 2540 49

Progeria is a globally noticed rare genetic disorder manifested by premature aging with no effective treatment. Under these circumstances, farnesyltransferase inhibitors (FTIs) are marked as promising drug candidates. Correspondingly, a pharmacophore model was generated exploiting the features of lonafarnib. The selected pharmacophore model was allowed to screen the InterBioScreen natural compound database to retrieve the potential lead candidates. A series of filtering steps were applied to assess the drug-likeness of the compounds. The obtained compounds were advanced to molecular docking employing the CDOCKER module available with Discovery Studio (DS). Subsequently, three compounds (Hits) have displayed a higher dock score and demonstrated key residue interactions with stable molecular dynamics simulation results compared to the reference compound. Taken together, we therefore put forth three identified Hits as FTIs that may further serve as chemical spaces in designing new compounds.
ACS Omega 2020 Feb 04
PMID:Discovery of Lonafarnib-Like Compounds: Pharmacophore Modeling and Molecular Dynamics Studies. 3203 12