20.500.12556/RUL-175861 Mechanistic insight into the dynamics of Mur ligase through a comprehensive timescale-specific approach Muramyl ligases are multidomain enzymes involved in intracellular steps of bacterial peptidoglycan synthesis and are considered promising targets for the development of new antibacterial agents. Among them, Mur ligase D (MurD) has been most widely used for structure-based design, but success has been limited. Here, we determine the $^{15}$ NMR spin relaxation parameters of apo and bound states of MurD in solution. We introduce a principal component analysis of the spectral densities derived from the NMR relaxation data, which provides a mechanistic insight into the dynamic events at the residue level. Compensation effects (ps-ms timescale) and conformational exchange dynamics (µs-ms timescale), the latter also measured independently, were revealed in bound and unbound MurD, which should be considered in the design of structurally novel Mur inhibitors. The mechanistic consideration used in our study can be broadly applicable to other systems for deciphering their specific dynamic mechanisms. ligases solution-state NMR muramil ligaze sinteza bakterijskih peptidoglikanov MurD ligaza NMR v raztopini farmacevtska kemija true false true Angleški jezik Slovenski jezik Članek v reviji 2025-11-11 11:36:57 2025-11-11 11:37:01 2025-12-15 04:09:27 0000-00-00 00:00:00 2025 0 0 15 str. [article no.] ǂ285 Vol. 8 2025 0000-00-00 Zaloznikova Objavljeno NiDoloceno 0000-00-00 0000-00-00 0000-00-00 615.4:54 2399-3669 10.1038/s42004-025-01675-z 250979587 s42004-025-01675-z_(1).pdf s42004-025-01675-z_(1).pdf 1 539F94666979E8A301BD569535BCA528 5820e7888a5bda49dfd063dd81fecd65fc8534440153afdf901a7a9d3a4dab80 b444a7f9-beea-11f0-9328-0050569b8976 https://repozitorij.uni-lj.si/Dokument.php?lang=slv&id=221774 https://www.nature.com/articles/s42004-025-01675-z 1 0ad282f1-beea-11f0-9328-0050569b8976 https://repozitorij.uni-lj.si/Dokument.php?lang=slv&id=221773 Fakulteta za farmacijo Medicinska fakulteta 0 0 0