2b0q

Crystal Structure Of 3',5"-Aminoglycoside Phosphotransferase Type IIIa ADP Neomycin B Complex

spinqualitylabelsall models 2b0q, resolution 2.70Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 2b0q is a 1 chain structure with sequence from "enterococcus_proteiformis"_thiercelin_and_jouhaud_1903 "enterococcus proteiformis" thiercelin and jouhaud 1903. This structure supersedes the now removed PDB entry 1l8u. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance. Ligands: ADP, MG, NMY Related: 1j7i, 1j7l, 1j7u, 1l8t Gene: aphA ("Enterococcus proteiformis" Thiercelin and Jouhaud 1903) Activity: Kanamycin kinase, with EC number 2.7.1.95 Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT Function [KKA3_ENTFL] Resistance to kanamycin and structurally-related aminoglycosides, including amikacin. Evolutionary Conservation Check, as determined by ConSurfDB. You may read the explanation of the method and the full data available from ConSurf. Publication Abstract from PubMed 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. 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 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See Also Phosphotransferase 3D structures

Proteopedia Page Contributors and Editors (what is this?)

OCA