8APV
Crystal Structure of H. influenzae TrmD in complex with Compound 27
Summary for 8APV
| Entry DOI | 10.2210/pdb8apv/pdb |
| Descriptor | tRNA (guanine-N(1)-)-methyltransferase, 1-[[4-(aminomethyl)phenyl]methyl]pyrrolo[2,3-b]pyridine-5-carboxamide, CITRIC ACID, ... (4 entities in total) |
| Functional Keywords | methyltransferase, rna binding protein |
| Biological source | Haemophilus influenzae |
| Total number of polymer chains | 1 |
| Total formula weight | 30222.46 |
| Authors | Hall, G.,Cowan, R.,Carr, M.D. (deposition date: 2022-08-10, release date: 2023-06-14, Last modification date: 2024-02-07) |
| Primary citation | 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 Cited by 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: 37187252DOI: 10.1016/j.bmcl.2023.129331 PDB entries with the same primary citation |
| Experimental method | X-RAY DIFFRACTION (2.4 Å) |
Structure validation
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