Thermodynamic Studies of Aminoglycoside Antibiotic-<br /> Enzyme Interactions
Journal Title: Türk Biyokimya Dergisi/Turkish Journal of Biochemistry - Year 2006, Vol 31, Issue 2
Abstract
In this manuscript, 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 these antibiotics are described. These studies revealed certain general properties of these complexes. Formation of the binary enzyme –AG complexes enthalpically favored and entropically disfavored. However, large exothermic enthalpy compensates the unfavorable entropy yielding a favorable free energy (.G) 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 enthalpy (.Hint) suggested that, at high pH, protonation of amino groups was the major contributor to .Hint, however, at neutral pH contributions from protonation/deprotonation of other functional groups were also involved.
Authors and Affiliations
Engin Serpersu , Can Özen , Edward Wright
Keywords
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