7BVA

Crystal structure of UDP-N-acetylmuramic Acid L-alanine ligase (MurC) from Mycobacterium bovis

Summary for 7BVA

• Entry DOI: 10.2210/pdb7bva/pdb
• Descriptor: UDP-N-acetylmuramate--L-alanine ligase, ZINC ION (3 entities in total)
• Functional Keywords: murc, peptidoglycan, ligase
• Biological source: Mycobacterium bovis (strain ATCC BAA-935 / AF2122/97) (Mycobacterium tuberculosis variant bovis AF2122/97)
• Total number of polymer chains: 2
• Total formula weight: 108936.31

Authors

Seo, P.W.,Kim, J.S. (deposition date: 2020-04-10, release date: 2020-04-22, Last modification date: 2023-11-29)

Primary citation

Seo, P.W.,Park, S.Y.,Hofmann, A.,Kim, J.S.
Crystal structures of UDP-N-acetylmuramic acid L-alanine ligase (MurC) from Mycobacterium bovis with and without UDP-N-acetylglucosamine.
Acta Crystallogr D Struct Biol, 77:618-627, 2021

PubMed Abstract: Peptidoglycan comprises repeating units of N-acetylmuramic acid, N-acetylglucosamine and short cross-linking peptides. After the conversion of UDP-N-acetylglucosamine (UNAG) to UDP-N-acetylmuramic acid (UNAM) by the MurA and MurB enzymes, an amino acid is added to UNAM by UDP-N-acetylmuramic acid L-alanine ligase (MurC). As peptidoglycan is an essential component of the bacterial cell wall, the enzymes involved in its biosynthesis represent promising targets for the development of novel antibacterial drugs. Here, the crystal structure of Mycobacterium bovis MurC (MbMurC) is reported, which exhibits a three-domain architecture for the binding of UNAM, ATP and an amino acid as substrates, with a nickel ion at the domain interface. The ATP-binding loop adopts a conformation that is not seen in other MurCs. In the UNAG-bound structure of MbMurC, the substrate mimic interacts with the UDP-binding domain of MbMurC, which does not invoke rearrangement of the three domains. Interestingly, the glycine-rich loop of the UDP-binding domain of MbMurC interacts through hydrogen bonds with the glucose moiety of the ligand, but not with the pyrophosphate moiety. These findings suggest that UNAG analogs might serve as potential candidates for neutralizing the catalytic activity of bacterial MurC.

PubMed: 33950018
DOI: 10.1107/S2059798321002199

Experimental method

X-RAY DIFFRACTION (2.303 Å)