7MGT

Ftp from Treponema pallidum bound to an ADP-like inhibitor

7MGT の概要

• エントリーDOI: 10.2210/pdb7mgt/pdb
• 分子名称: FAD:protein FMN transferase, MAGNESIUM ION, 2-chloroadenosine 5'-(trihydrogen diphosphate), ... (5 entities in total)
• 機能のキーワード: hydrolase, hydrolase-hydrolase inhibitor complex, hydrolase/hydrolase inhibitor
• 由来する生物種: Treponema pallidum
• タンパク質・核酸の鎖数: 1
• 化学式量合計: 40964.17

構造登録者

Brautigam, C.A.,Deka, R.,Norgard, M.V. (登録日: 2021-04-13, 公開日: 2021-12-08, 最終更新日: 2023-10-18)

主引用文献

Deka, R.K.,Deka, A.,Liu, W.Z.,Norgard, M.V.,Brautigam, C.A.
Inhibition of bacterial FMN transferase: A potential avenue for countering antimicrobial resistance.
Protein Sci., 31:545-551, 2022

PubMed Abstract: Antibiotic resistance is a challenge for the control of bacterial infections. In an effort to explore unconventional avenues for antibacterial drug development, we focused on the FMN-transferase activity of the enzyme Ftp from the syphilis spirochete, Treponema pallidum (Ftp_Tp). This enzyme, which is only found in prokaryotes and trypanosomatids, post-translationally modifies proteins in the periplasm, covalently linking FMN (from FAD) to proteins that typically are important for establishing an essential electrochemical gradient across the cytoplasmic membrane. As such, Ftp inhibitors potentially represent a new class of antimicrobials. Previously, we showed that AMP is both a product of the Ftp_tp-catalyzed reaction and an inhibitor of the enzyme. As a preliminary step in exploiting this property to develop a novel Ftp_Tp inhibitor, we have used structural and solution studies to examine the inhibitory and enzyme-binding properties of several adenine-based nucleosides, with particular focus on the 2-position of the purine ring. Implications for future drug design are discussed.

PubMed: 34796555
DOI: 10.1002/pro.4241

実験手法

X-RAY DIFFRACTION (1.54 Å)