8APV

Crystal Structure of H. influenzae TrmD in complex with Compound 27

8APV の概要

• エントリーDOI: 10.2210/pdb8apv/pdb
• 分子名称: tRNA (guanine-N(1)-)-methyltransferase, 1-[[4-(aminomethyl)phenyl]methyl]pyrrolo[2,3-b]pyridine-5-carboxamide, CITRIC ACID, ... (4 entities in total)
• 機能のキーワード: methyltransferase, rna binding protein
• 由来する生物種: Haemophilus influenzae
• タンパク質・核酸の鎖数: 1
• 化学式量合計: 30222.46

構造登録者

Hall, G.,Cowan, R.,Carr, M.D. (登録日: 2022-08-10, 公開日: 2023-06-14, 最終更新日: 2024-02-07)

主引用文献

Wilkinson, A.J.,Ooi, N.,Finlayson, J.,Lee, V.E.,Lyth, D.,Maskew, K.S.,Newman, R.,Orr, D.,Ansell, K.,Birchall, K.,Canning, P.,Coombs, P.,Fusani, L.,McIver, E.,Pisco, J.,Ireland, P.M.,Jenkins, C.,Norville, I.H.,Southern, S.J.,Cowan, R.,Hall, G.,Kettleborough, C.,Savage, V.J.,Cooper, I.R.
Evaluating the druggability of TrmD, a potential antibacterial target, through design and microbiological profiling of a series of potent TrmD inhibitors.
Bioorg.Med.Chem.Lett., 90:129331-129331, 2023

PubMed Abstract: The post-transcriptional modifier tRNA-(NG37) methyltransferase (TrmD) has been proposed to be essential for growth in many Gram-negative and Gram-positive pathogens, however previously reported inhibitors show only weak antibacterial activity. In this work, optimisation of fragment hits resulted in compounds with low nanomolar TrmD inhibition incorporating features designed to enhance bacterial permeability and covering a range of physicochemical space. The resulting lack of significant antibacterial activity suggests that whilst TrmD is highly ligandable, its essentiality and druggability are called into question.

PubMed: 37187252
DOI: 10.1016/j.bmcl.2023.129331

実験手法

X-RAY DIFFRACTION (2.4 Å)