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Catalytic Site Atlas Version 2.2.12
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CSA entry for 1l8t
Original Entry
Title:
Transferase
Compound:
Aminoglycoside 3'-phosphotransferase
Mutant:
No
UniProt/Swiss-Prot:
P00554-KKA3_ENTFA
EC Class:
2.7.1.95
Other CSA Entries:
Overview of all sites for 1l8t
Homologues of 1l8t
Entries for UniProt/Swiss-Prot: P00554
Entries for EC: 2.7.1.95
Other Databases:
PDB entry: 1l8t
PDBsum entry: 1l8t
UniProt/Swiss-Prot: P00554
IntEnz entry: 2.7.1.95
Literature Report:
Introduction:
Aminoglycosides 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.
Mechanism:
Nucleophilic 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.
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Found by:
Literature reference 

ResidueChainNumberUniProt numberFunctional part FunctionTargetDescription
LYSA 44 44Sidechain
ElectrostaticTransition state
Contacts 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.
Evidence from paper Evidence concerns Evidence type
PubMed ID 9200607 Current protein Residue is positioned appropriately (ligand position hypothetical)
PubMed ID 9200607 Current protein Mutagenesis of residue
PubMed ID 9200607 Current protein Structural similarity to homologue of known mechanism

ResidueChainNumberUniProt numberFunctional part FunctionTargetDescription
ASPA 190 190Sidechain
Acid/baseSubstrate
Acts to deprotonate the attacking OH group to allow it to act as a nucleophile and form a bond to the gamma phosphate of ATP.
Evidence from paper Evidence concerns Evidence type
PubMed ID 9200607 Current protein Residue is positioned appropriately (ligand position hypothetical)
PubMed ID 9200607 Current protein Conservation of residue
PubMed ID 9200607 Current protein Mutagenesis of residue
References:
1
Structure of an enzyme required for aminoglycoside antibiotic resistance reveals homology to eukaryotic protein kinases.
W. C. Hon and G. A. McKay and P. R. Thompson and R. M. Sweet and D. S. Yang and G. D. Wright and A. M. Berghuis
Cell 89, (6) 887-95, (1997).
9200607
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