1L8T
Crystal Structure Of 3',5"-Aminoglycoside Phosphotransferase Type IIIa ADP Kanamycin A Complex
Summary for 1L8T
| Entry DOI | 10.2210/pdb1l8t/pdb |
| Related | 1J7I 1J7L 1J7U |
| Descriptor | Aminoglycoside 3'-Phosphotransferase, MAGNESIUM ION, ADENOSINE-5'-DIPHOSPHATE, ... (5 entities in total) |
| Functional Keywords | transferase |
| Biological source | Enterococcus faecalis |
| Total number of polymer chains | 1 |
| Total formula weight | 31841.16 |
| Authors | Fong, D.H.,Berghuis, A.M. (deposition date: 2002-03-21, release date: 2002-06-19, Last modification date: 2024-02-14) |
| Primary citation | Fong, D.H.,Berghuis, A.M. Substrate promiscuity of an aminoglycoside antibiotic resistance enzyme via target mimicry. EMBO J., 21:2323-2331, 2002 Cited by PubMed Abstract: 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. PubMed: 12006485DOI: 10.1093/emboj/21.10.2323 PDB entries with the same primary citation |
| Experimental method | X-RAY DIFFRACTION (2.4 Å) |
Structure validation
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