7MGT

Ftp from Treponema pallidum bound to an ADP-like inhibitor

Summary for 7MGT

• Entry DOI: 10.2210/pdb7mgt/pdb
• Descriptor: FAD:protein FMN transferase, MAGNESIUM ION, 2-chloroadenosine 5'-(trihydrogen diphosphate), ... (5 entities in total)
• Functional Keywords: hydrolase, hydrolase-hydrolase inhibitor complex, hydrolase/hydrolase inhibitor
• Biological source: Treponema pallidum
• Total number of polymer chains: 1
• Total formula weight: 40964.17

Authors

Brautigam, C.A.,Deka, R.,Norgard, M.V. (deposition date: 2021-04-13, release date: 2021-12-08, Last modification date: 2023-10-18)

Primary citation

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

Experimental method

X-RAY DIFFRACTION (1.54 Å)