Mechanistic insight into the dynamics of Mur ligase through a comprehensive timescale-specific approach

Ogris, Iza (avtor), Zupančič, Barbara (avtor), Sosič, Izidor (avtor), Merzel, Franci (avtor), Golič Grdadolnik, Simona (avtor)

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.

• Jezik: Angleški jezik
• Ključne besede: ligases, solution-state NMR
• Vrsta gradiva: Članek v reviji
• Tipologija: 1.01 - Izvirni znanstveni članek
• Organizacija: FFA - Fakulteta za farmacijo ; MF - Medicinska fakulteta
• Status publikacije: Objavljeno
• Različica publikacije: Objavljena publikacija
• Leto izida: 2025
• Št. strani: 15 str.
• Številčenje: Vol. 8, [article no.] ǂ285
• PID: 20.500.12556/RUL-175861
• UDK: 615.4:54
• ISSN pri članku: 2399-3669
• DOI: 10.1038/s42004-025-01675-z
• COBISS.SI-ID: 250979587
• Datum objave v RUL: 11.11.2025

Gradivo je del revije

• Naslov: Communications chemistry
• Skrajšan naslov: Commun. chem.
• Založnik: Macmillan Publishers, part of Springer Nature
• ISSN: 2399-3669
• COBISS.SI-ID: 529716505

Licence

• Licenca: CC BY 4.0, Creative Commons Priznanje avtorstva 4.0 Mednarodna
• Povezava: http://creativecommons.org/licenses/by/4.0/deed.sl
• Opis: To je standardna licenca Creative Commons, ki daje uporabnikom največ možnosti za nadaljnjo uporabo dela, pri čemer morajo navesti avtorja.

Sekundarni jezik

• Jezik: Slovenski jezik
• Ključne besede: muramil ligaze, sinteza bakterijskih peptidoglikanov, MurD ligaza, NMR v raztopini, farmacevtska kemija