1l8t

From Proteopedia

---

Revision as of 18:15, 20 November 2007

proteopedia linkproteopedia link

spinqualitylabelsall models 1l8t, resolution 2.4Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image

Crystal Structure Of 3',5"-Aminoglycoside Phosphotransferase Type IIIa ADP Kanamycin A 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

1L8T is a Single protein structure of sequence from Enterococcus faecalis with MG, ADP and KAN as ligands. 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 Tue Nov 20 20:22:48 2007