Revealing the Mechanism of Binding Selectivity in Undecaprenyl Diphosphate Synthase
نویسندگان
چکیده
منابع مشابه
Undecaprenyl Diphosphate Synthase Inhibitors: Antibacterial Drug Leads
There is a significant need for new antibiotics due to the rise in drug resistance. Drugs such as methicillin and vancomycin target bacterial cell wall biosynthesis, but methicillin-resistant Staphylococcus aureus (MRSA) and vancomycin-resistant Enterococci (VRE) have now arisen and are of major concern. Inhibitors acting on new targets in cell wall biosynthesis are thus of particular interest ...
متن کاملMolecular cloning, expression, and purification of undecaprenyl diphosphate synthase. No sequence similarity between E- and Z-prenyl diphosphate synthases.
Cloning of the gene for undecaprenyl diphosphate synthase was successful, providing the first primary structure for any prenyltransferase that catalyzes Z-prenyl chain elongation. A genomic DNA library of Micrococcus luteus B-P 26 was constructed in Escherichia coli, and the recombinant clones were grown on nylon membranes. The membrane was incubated directly by floating it on a reaction mixtur...
متن کاملAntagonism screen for inhibitors of bacterial cell wall biogenesis uncovers an inhibitor of undecaprenyl diphosphate synthase.
Drug combinations are valuable tools for studying biological systems. Although much attention has been given to synergistic interactions in revealing connections between cellular processes, antagonistic interactions can also have tremendous value in elucidating genetic networks and mechanisms of drug action. Here, we exploit the power of antagonism in a high-throughput screen for molecules that...
متن کاملCrystal structure of cis-prenyl chain elongating enzyme, undecaprenyl diphosphate synthase.
Undecaprenyl diphosphate synthase (UPS) catalyzes the cis-prenyl chain elongation onto trans, trans-farnesyl diphosphate (FPP) to produce undecaprenyl diphosphate (UPP), which is indispensable for the biosynthesis of bacterial cell walls. We report here the crystal structure of UPS as the only three-dimensional structure among cis-prenyl chain elongating enzymes. The structure is classified int...
متن کاملTaxodione and arenarone inhibit farnesyl diphosphate synthase by binding to the isopentenyl diphosphate site.
We used in silico methods to screen a library of 1,013 compounds for possible binding to the allosteric site in farnesyl diphosphate synthase (FPPS). Two of the 50 predicted hits had activity against either human FPPS (HsFPPS) or Trypanosoma brucei FPPS (TbFPPS), the most active being the quinone methide celastrol (IC50 versus TbFPPS ∼ 20 µM). Two rounds of similarity searching and activity tes...
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ژورنال
عنوان ژورنال: Biophysical Journal
سال: 2017
ISSN: 0006-3495
DOI: 10.1016/j.bpj.2016.11.1719