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EC Number

Catalytic Site Atlas

CSA LITERATURE entry for 1l8t

E.C. namekanamycin kinase
SpeciesEnterococcus faecalis (Streptococcus faecalis)
E.C. Number (IntEnz)
CSA Homologues of 1l8tThere are 33 Homologs
CSA Entries With UniProtID P0A3Y5
CSA Entries With EC Number
PDBe Entry 1l8t
PDBSum Entry 1l8t
MACiE Entry 1l8t

Literature Report

IntroductionAminoglycosides are potent antibiotics which bind to the prokaryotic 16S ribosomal subunit, inhibiting protein synthesis. Resistance to these antibiotics however has developed in many bacterial species due to the enzyme aminoglycoside kinase which is able to catalyse the phosphorylation of the aminoglycoside resulting in its inactivation. Therefore kinetic and structural studies of this enzyme are vital in prevention and understanding of antibiotic resistance. The enzyme shows structural alignment, despite very low sequence conservation, to eukaryotic protein kinases indicating a possible evolutionary relationship.
MechansimNucleophilic attack on the gamma phosphate of ATP by the 3' or 5'' OH group of the substrate allows formation of a pentavalent phosphate transition state which collapses to release the products. In order to accelerate this the deprotonation of the OH group is accomplished by Asp 190 and the transition state is stabilised by contact with Lys 44.

Catalytic Sites for 1l8t

Annotated By Reference To The Literature - Site 1 (Perform Site Search)
ResidueChainNumberUniProtKB NumberFunctional PartFunctionTargetDescription
LysA4444macie:sideChainContacts the beta and gamma phosphates of ATP, thus is positioned to stabilise the negative charge that builds up when the pentavalent phosphate transition state forms.
AspA190190macie:sideChainActs to deprotonate the attacking OH group to allow it to act as a nucleophile and form a bond to the gamma phosphate of ATP.

Literature References

Hon WC
Structure of an enzyme required for aminoglycoside antibiotic resistance reveals homology to eukaryotic protein kinases.
Cell 1997 89 887-895
PubMed: 9200607