3SG9

Crystal Structure of Aminoglycoside-2''-Phosphotransferase Type IVa Kanamycin A Complex

3SG9 の概要

• エントリーDOI: 10.2210/pdb3sg9/pdb
• 分子名称: APH(2'')-Id, KANAMYCIN A, CHLORIDE ION, ... (4 entities in total)
• 機能のキーワード: antibiotic resistance enzyme, transferase, aminoglycoside, phosphotransferase, transferase-antibiotic complex, transferase/antibiotic
• 由来する生物種: Enterococcus casseliflavus
• タンパク質・核酸の鎖数: 2
• 化学式量合計: 72543.66

構造登録者

Shi, K.,Houston, D.R.,Berghuis, A.M. (登録日: 2011-06-14, 公開日: 2011-06-29, 最終更新日: 2024-02-28)

主引用文献

Shi, K.,Houston, D.R.,Berghuis, A.M.
Crystal Structures of Antibiotic-Bound Complexes of Aminoglycoside 2''-Phosphotransferase IVa Highlight the Diversity in Substrate Binding Modes among Aminoglycoside Kinases.
Biochemistry, 50:6237-6244, 2011

PubMed Abstract: Aminoglycoside 2''-phosphotransferase IVa [APH(2'')-IVa] is a member of a family of bacterial enzymes responsible for medically relevant resistance to antibiotics. APH(2'')-IVa confers high-level resistance against several clinically used aminoglycoside antibiotics in various pathogenic Enterococcus species by phosphorylating the drug, thereby preventing it from binding to its ribosomal target and producing a bactericidal effect. We describe here three crystal structures of APH(2'')-IVa, one in its apo form and two in complex with a bound antibiotic, tobramycin and kanamycin A. The apo structure was refined to a resolution of 2.05 Å, and the APH(2'')-IVa structures with tobramycin and kanamycin A bound were refined to resolutions of 1.80 and 2.15 Å, respectively. Comparison among the structures provides insight concerning the substrate selectivity of this enzyme. In particular, conformational changes upon substrate binding, involving rotational shifts of two distinct segments of the enzyme, are observed. These substrate-induced shifts may also rationalize the altered substrate preference of APH(2'')-IVa in comparison to those of other members of the APH(2'') subfamily, which are structurally closely related. Finally, analysis of the interactions between the enzyme and aminoglycoside reveals a distinct binding mode as compared to the intended ribosomal target. The differences in the pattern of interactions can be utilized as a structural basis for the development of improved aminoglycosides that are not susceptible to these resistance factors.

PubMed: 21678960
DOI: 10.1021/bi200747f

実験手法

X-RAY DIFFRACTION (2.15 Å)