Linked Life Data

20387903

Source:http://linkedlifedata.com/resource/pubmed/id/20387903

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
19
pubmed:dateCreated
2010-5-11
pubmed:abstractText
The thermodynamic and kinetic properties of interactions of antibiotics with the aminoglycoside acetyltransferase (3)-IIIb (AAC) are determined with several experimental methods. These data represent the first such characterization of an enzyme that modifies the 2-deoxystreptamine ring common to all aminoglycoside antibiotics. Antibiotic substrates for AAC include kanamycin A, kanamycin B, tobramycin, sisomicin, neomycin B, paromomycin, lividomycin A, and ribostamycin. Kinetic studies show that kanamycin group aminoglycosides have higher k(cat) values than members of the neomycin group. Only small aminoglycosides without intraring constraints show substrate inhibition. Isothermal titration calorimetry (ITC) and fluorescence measurements are consistent with a molecular size-dependent stoichiometry where binding stoichiometries are 1.5-2.0 for small antibiotics and 1.0 for larger. Antibiotic-enzyme interaction occurs with a favorable enthalpy (DeltaH < 0) and a compensating unfavorable entropy (TDeltaS < 0). The presence of coenzyme A significantly increases the affinity of the antibiotic for AAC. However, the thermodynamic properties of its ternary complexes distinguish this enzyme from other aminoglycoside-modifying enzymes (AGMEs). Unlike other AGMEs, the enthalpy of binding becomes more favored by 1.7-10.0-fold in the presence of the cosubstrate CoASH, while the entropy becomes 2.0-22.5-fold less favored. The overall free energy change is still only 1.0-1.9 kcal/mol from binary to ternary for all antibiotics tested, which is similar to those for other aminoglycoside-modifying enzymes. A computationally derived homology model provides structural support for these conclusions and further indicates that AAC is likely a member of the GCN5-related acetyltransferase family of proteins.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
May
pubmed:issn
1520-4995
pubmed:author
pubmed:issnType
Electronic
pubmed:day
18
pubmed:volume
49
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
4027-35
pubmed:meshHeading
pubmed:year
2010
pubmed:articleTitle
Thermodynamics and kinetics of association of antibiotics with the aminoglycoside acetyltransferase (3)-IIIb, a resistance-causing enzyme.
pubmed:affiliation
Department of Biochemistry and Cellular and Molecular Biology, The University of Tennessee, Knoxville, Tennessee 37996, USA.
pubmed:publicationType
Journal Article, Research Support, U.S. Gov't, Non-P.H.S., Research Support, Non-U.S. Gov't