Michał Zieliński

Enzyme-mediated aminoglycoside resistance without target mimicry

Mark Hemmings, Michał Zieliński, Tolou Golkar, Jonathan Blanchet et autres

The primary mode of resistance to aminoglycoside antibiotics is through chemical modification catalyzed by aminoglycoside-modifying enzymes. Numerous structural studies of these enzymes have invariably shown that they bind aminoglycosides in the same lowest-energy conformation as the intended target for these antibiotics, the …

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Structural elucidation of substrate-bound aminoglycoside acetyltransferase (3)-IIIa

Michał Zieliński, Jonathan Blanchet, Sophia Hailemariam, Albert Marinus Berghuis

Canonical aminoglycosides are a large group of antibiotics, where the part of chemical diversity stems from the substitution of the neamine ring system on positions 5 and 6. Certain aminoglycoside modifying enzymes can modify a broad range of 4,5- and 4,6-disubstituted aminoglycosides, …

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Structural and functional insights into esterase-mediated macrolide resistance

Michał Zieliński, Jaeok Park, Barry Sleno, Albert Marinus Berghuis

Macrolides are a class of antibiotics widely used in both medicine and agriculture. Unsurprisingly, as a consequence of their exensive usage a plethora of resistance mechanisms have been encountered in pathogenic bacteria. One of these resistance mechanisms entails the enzymatic cleavage of …

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Look and Outlook on Enzyme-Mediated Macrolide Resistance

Tolou Golkar, Michał Zieliński, Albert Marinus Berghuis

Since their discovery in the early 1950s, macrolide antibiotics have been used in both agriculture and medicine. Specifically, macrolides such as erythromycin and azithromycin have found use as substitutes for β-lactam antibiotics in patients with penicillin allergies. Given the extensive use of …

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Human farnesyl pyrophosphate synthase is allosterically inhibited by its own product

Jaeok Park, Michał Zieliński, Alexandr Magder, Youla S. Tsantrizos et autres

Abstract Farnesyl pyrophosphate synthase (FPPS) is an enzyme of the mevalonate pathway and a well-established therapeutic target. Recent research has focused around a newly identified druggable pocket near the enzyme’s active site. Pharmacological exploitation of this pocket is deemed promising; however, its …

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Probing the molecular and structural elements of ligands binding to the active site versus an allosteric pocket of the human farnesyl pyrophosphate synthase

Dimitrios Gritzalis, Jaeok Park, Wei Chiu, Hyungjun Cho et autres

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