2b0q
From Proteopedia
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Crystal Structure Of 3',5"-Aminoglycoside Phosphotransferase Type IIIa ADP Neomycin B Complex
Overview
The misuse of antibiotics has selected for bacteria that have evolved, mechanisms for evading the effects of these drugs. For aminoglycosides, a, group of clinically important bactericidal antibiotics that target the, A-site of the 16S ribosomal RNA, the most common mode of resistance is, enzyme-catalyzed chemical modification of the drug. While aminoglycosides, are structurally diverse, a single enzyme can confer resistance to many of, these antibiotics. For example, the aminoglycoside kinase APH(3')-IIIa, produced by pathogenic Gram-positive bacteria such as enterococci and, staphylococci, is capable of detoxifying at least 10 distinct, aminoglycosides. Here we describe the crystal structures of APH(3')-IIIa, in complex with ADP and kanamycin A or neomycin B. These structures reveal, that the basis for this enzyme's substrate promiscuity is the presence of, two alternative subsites in the antibiotic binding pocket. Furthermore, comparison between the A-site of the bacterial ribosome and APH(3')-IIIa, shows that mimicry is the second major factor in dictating the substrate, spectrum of APH(3')-IIIa. These results suggest a potential strategy for, drug design aimed at circumventing antibiotic resistance.
About this Structure
2B0Q is a Single protein structure of sequence from Enterococcus faecalis with MG, ADP and NMY as ligands. This structure superseeds the now removed PDB entry 1L8U. Active as Kanamycin kinase, with EC number 2.7.1.95 Full crystallographic information is available from OCA.
Reference
Substrate promiscuity of an aminoglycoside antibiotic resistance enzyme via target mimicry., Fong DH, Berghuis AM, EMBO J. 2002 May 15;21(10):2323-31. PMID:12006485
Page seeded by OCA on Wed Nov 21 08:30:22 2007
