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Thermodynamic Studies of Aminoglycoside Antibiotic-Enzyme Interactions

Author(s): Engin H. Serpersu | Can Özen, | Edward Wright1

Journal: Türk Biyokimya Dergisi
ISSN 0250-4685

Volume: 31;
Issue: 2;
Start page: 79;
Date: 2006;
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Keywords: Aminoglycosides | Aminoglycoside-Modifying Enzymes | Thermodynamics | E | Enzyme–Aminoglycoside C e Complexes

In this manuscrip ipt, we describe thermodynamic properties of complexes formed between aminoglycoside antibiotics and the enzymes that modify these antibiotics and render them useless against infectious bacteria. Studies with three different enzymes that represent three different catalytic modification reactions for theseantibiotics are described. These studies revealed certain general properties of these complexes. Formation of the binary enzyme –AG complexes enthalp lpically favored and entropically disfavored. However, large exothermic enthalp lpy compensates theunfavorable entropy yielding a favorable free energy (ΔG) of binding in all cases.The presence of co-substrate increases the affinity of AGs to enzymes. A general selectivity pattern for aminoglycosides were also revealed from these studies such that the aminoglycosides with 2’-NH2 and 6’-NH2 bind to enzymes with higher affinity when compared to those with – OH at these positions.Binding-linked protonation is also observed in the formation of binary enzyme– aminoglycoside and ternary enzyme–co-substrate–AG complexes. Multiple amino groups of aminoglycosides show up-shifted pKas in enzyme–aminoglycoside complexes compared to free aminoglycosides. Determined intrinsic enthalp lpy(ΔHint) suggested that, at high pH, protonation of amino groups was the major contributor to ΔHint, however, at neutral pH contributions from protonation/ deprotonation of other functional groups were also involved.
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