1KNY

KANAMYCIN NUCLEOTIDYLTRANSFERASE

1KNY の概要

• エントリーDOI: 10.2210/pdb1kny/pdb
• 分子名称: KANAMYCIN NUCLEOTIDYLTRANSFERASE, MAGNESIUM ION, DIPHOSPHOMETHYLPHOSPHONIC ACID ADENOSYL ESTER, ... (5 entities in total)
• 機能のキーワード: antibiotic resistance, transferase, plasmid
• 由来する生物種: Staphylococcus aureus
• タンパク質・核酸の鎖数: 2
• 化学式量合計: 59775.25

構造登録者

Pedersen, L.C.,Benning, M.M.,Holden, H.M. (登録日: 1995-07-07, 公開日: 1996-08-17, 最終更新日: 2024-02-14)

主引用文献

Pedersen, L.C.,Benning, M.M.,Holden, H.M.
Structural investigation of the antibiotic and ATP-binding sites in kanamycin nucleotidyltransferase.
Biochemistry, 34:13305-13311, 1995

PubMed Abstract: Kanamycin nucleotidyltransferase (KNTase) is a plasmid-coded enzyme responsible for some types of bacterial resistance to aminoglycosides. The enzyme deactivates various antibiotics by transferring a nucleoside monophosphate group from ATP to the 4'-hydroxyl group of the drug. Detailed knowledge of the interactions between the protein and the substrates may lead to the design of aminoglycosides less susceptible to bacterial deactivation. Here we describe the structure of KNTase complexed with both the nonhydrolyzable nucleotide analog AMPCPP and kanamycin. Crystals employed in the investigation were grown from poly(ethylene glycol) solutions and belonged to the space group P2(1)2(1)2(1) with unit cell dimensions of a = 57.3 A, b = 102.2 A, c = 101.8 A, and one dimer in the asymmetric unit. Least-squares refinement of the model at 2.5 A resolution reduced the crystallographic R factor to 16.8%. The binding pockets for both the nucleotide and the antibiotic are extensively exposed to the solvent and are composed of amino acid residues contributed by both subunits in the dimer. There are few specific interactions between the protein and the adenine ring of the nucleotide; rather the AMPCPP molecule is locked into position by extensive hydrogen bonding between the alpha-, beta-, and gamma-phosphates and protein side chains. This, in part, may explain the observation that the enzyme can utilize other nucleotides such as GTP and UTP. The 4'-hydroxyl group of the antibiotic is approximately 5 A from the alpha-phosphorus of the nucleotide and is in the proper orientation for a single in-line displacement attack at the phosphorus.(ABSTRACT TRUNCATED AT 250 WORDS)

PubMed: 7577914
DOI: 10.1021/bi00041a005

実験手法

X-RAY DIFFRACTION (2.5 Å)