5IQC

Aminoglycoside Phosphotransferase (2'')-Ia (CTD of AAC(6')-Ie/APH(2'')-Ia) in complex with GMPPNP, Magnesium, and Gentamicin C1

5IQC の概要

• エントリーDOI: 10.2210/pdb5iqc/pdb
• 関連するPDBエントリー: 5BYL 5IQA 5IQB 5IQD 5IQE 5IQF 5IQG 5IQH 5IQI
• 分子名称: Bifunctional AAC/APH, PHOSPHOAMINOPHOSPHONIC ACID-GUANYLATE ESTER, gentamicin C1, ... (7 entities in total)
• 機能のキーワード: kinase, antibiotic, aminoglycoside, resistance, transferase
• 由来する生物種: Staphylococcus aureus
• タンパク質・核酸の鎖数: 4
• 化学式量合計: 148301.25

構造登録者

Caldwell, S.J.,Berghuis, A.M. (登録日: 2016-03-10, 公開日: 2016-05-25, 最終更新日: 2023-09-27)

主引用文献

Caldwell, S.J.,Huang, Y.,Berghuis, A.M.
Antibiotic Binding Drives Catalytic Activation of Aminoglycoside Kinase APH(2)-Ia.
Structure, 24:935-945, 2016

PubMed Abstract: APH(2″)-Ia is a widely disseminated resistance factor frequently found in clinical isolates of Staphylococcus aureus and pathogenic enterococci, where it is constitutively expressed. APH(2″)-Ia confers high-level resistance to gentamicin and related aminoglycosides through phosphorylation of the antibiotic using guanosine triphosphate (GTP) as phosphate donor. We have determined crystal structures of the APH(2″)-Ia in complex with GTP analogs, guanosine diphosphate, and aminoglycosides. These structures collectively demonstrate that aminoglycoside binding to the GTP-bound kinase drives conformational changes that bring distant regions of the protein into contact. These changes in turn drive a switch of the triphosphate cofactor from an inactive, stabilized conformation to a catalytically competent active conformation. This switch has not been previously reported for antibiotic kinases or for the structurally related eukaryotic protein kinases. This catalytic triphosphate switch presents a means by which the enzyme can curtail wasteful hydrolysis of GTP in the absence of aminoglycosides, providing an evolutionary advantage to this enzyme.

PubMed: 27161980
DOI: 10.1016/j.str.2016.04.002

実験手法

X-RAY DIFFRACTION (2.3 Å)