1F9G

CRYSTAL STRUCTURE OF STREPTOCOCCUS PNEUMONIAE HYALURONATE LYASE COCRYSTALLIZED WITH ASCORBIC ACID

1F9G の概要

• エントリーDOI: 10.2210/pdb1f9g/pdb
• 関連するPDBエントリー: 1egu 1f1s
• 分子名称: HYALURONATE LYASE, ASCORBIC ACID (3 entities in total)
• 機能のキーワード: ascorbic acid binds to the indole group of trp292, transmembrane, lyase
• 由来する生物種: Streptococcus pneumoniae
• 細胞内の位置: Secreted, cell wall; Peptidoglycan-anchor (Potential): Q54873
• タンパク質・核酸の鎖数: 1
• 化学式量合計: 83738.06

構造登録者

Li, S.,Jedrzejas, M.J. (登録日: 2000-07-10, 公開日: 2001-05-16, 最終更新日: 2024-05-22)

主引用文献

Li, S.,Taylor, K.B.,Kelly, S.J.,Jedrzejas, M.J.
Vitamin C inhibits the enzymatic activity of Streptococcus pneumoniae hyaluronate lyase.
J.Biol.Chem., 276:15125-15130, 2001

PubMed Abstract: Enzyme activity measurement showed that L-ascorbic acid (vitamin C (Vc)) competitively inhibits the hyaluronan degradation by Streptococcus pneumoniae hyaluronate lyase. The complex crystal structure of this enzyme with Vc was determined at 2.0 A resolution. One Vc molecule was found to bind to the active site of the enzyme. The Vc carboxyl group provides the negative charges that lead the molecule into the highly positively charged cleft of the enzyme. The Vc ring system forms hydrophobic interactions with the side chain of Trp-292, which is one of the aromatic patch residues of this enzyme responsible for the selection of the cleavage sites on the substrate chain. The binding of Vc inhibits the substrate binding at hyaluronan 1, 2, and 3 (HA1, HA2, and HA3) catalytic positions. The high concentration of Vc in human tissues probably provides a low level of natural resistance to the pneumococcal invasion. This is the first time that Vc the direct inhibition on the bacterial "spreading factor" was reported, and Vc is also the first chemical that has been shown experimentally to have an inhibitory effect on bacterial hyaluronate lyase. These studies also highlight the possible structural requirement for the design of a stronger inhibitor of bacterial hyaluronate lyase.

PubMed: 11278838
DOI: 10.1074/jbc.M011102200

実験手法

X-RAY DIFFRACTION (2 Å)