1J7U

Crystal Structure of 3',5"-Aminoglycoside Phosphotransferase Type IIIa AMPPNP Complex

1J7U の概要

• エントリーDOI: 10.2210/pdb1j7u/pdb
• 関連するPDBエントリー: 1J7I 1J7L
• 分子名称: AMINOGLYCOSIDE 3'-PHOSPHOTRANSFERASE, MAGNESIUM ION, PHOSPHOAMINOPHOSPHONIC ACID-ADENYLATE ESTER, ... (4 entities in total)
• 機能のキーワード: antibiotic resistance, kinase, atp-binding, transferase
• 由来する生物種: Enterococcus faecalis
• タンパク質・核酸の鎖数: 2
• 化学式量合計: 63133.70

構造登録者

Burk, D.L.,Hon, W.C.,Leung, A.K.-W.,Berghuis, A.M. (登録日: 2001-05-18, 公開日: 2001-08-08, 最終更新日: 2024-11-13)

主引用文献

Burk, D.L.,Hon, W.C.,Leung, A.K.,Berghuis, A.M.
Structural analyses of nucleotide binding to an aminoglycoside phosphotransferase.
Biochemistry, 40:8756-8764, 2001

PubMed Abstract: 3',5"-Aminoglycoside phosphotransferase type IIIa [APH(3')-IIIa] is a bacterial enzyme that confers resistance to a range of aminoglycoside antibiotics while exhibiting striking homology to eukaryotic protein kinases (ePK). The structures of APH(3')-IIIa in its apoenzyme form and in complex with the nonhydrolyzable ATP analogue AMPPNP were determined to 3.2 and 2.4 A resolution, respectively. Furthermore, refinement of the previously determined ADP complex was completed. The structure of the apoenzyme revealed alternate positioning of a flexible loop (analogous to the P-loop of ePK's), occupying part of the nucleotide-binding pocket of the enzyme. Despite structural similarity to protein kinases, there was no evidence of domain movement associated with nucleotide binding. This rigidity is due to the presence of more extensive interlobe interactions in the APH(3')-IIIa structure than in the ePK's. Differences between the ADP and AMPPNP complexes are confined to the area of the nucleotide-binding pocket. The position of conserved active site residues and magnesium ions remains unchanged, but there are differences in metal coordination between the two nucleotide complexes. Comparison of the di/triphosphate binding site of APH(3')-IIIa with that of ePK's suggests that the reaction mechanism of APH(3")-IIIa and related aminoglycoside kinases will closely resemble that of eukaryotic protein kinases. However, the orientation of the adenine ring in the binding pocket differs between APH(3')-IIIa and the ePK's by a rotation of approximately 40 degrees. This alternate binding mode is likely a conserved feature among aminoglycoside kinases and could be exploited for the structure-based drug design of compounds to combat antibiotic resistance.

PubMed: 11467935
DOI: 10.1021/bi010504p

実験手法

X-RAY DIFFRACTION (2.4 Å)