Structural highlights
Function
[FEMX_STAAU] Catalyzes the incorporation of the first glycine of the pentaglycine interpeptide bridge, which is characteristic of the S.aureus peptidoglycan. This glycine is added to the epsilon-amino group of the L-lysine of the membrane-bound lipid II intermediate (GlcNAc-(beta-1,4)-N-acetylmuramic acid(-L-Ala-D-iGln-L-Lys-D-Ala-D-Ala)-pyrophosphoryl-undecaprenol), using glycyl-tRNA(Gly) as donor, in a ribosome-independent mechanism (By similarity).
Publication Abstract from PubMed
Branched Lipid II, required for the formation of indirectly crosslinked peptidoglycan, is generated by MurM, a protein essential for high-level penicillin resistance in the human pathogen Streptococcus pneumoniae. We have solved the X-ray crystal structure of Staphylococcus aureus FemX, an isofunctional homolog, and have used this as a template to generate a MurM homology model. Using this model, we perform molecular docking and molecular dynamics to examine the interaction of MurM with the phospholipid bilayer and the membrane-embedded Lipid II substrate. Our model suggests that MurM is associated with the major membrane phospholipid cardiolipin, and experimental evidence confirms that the activity of MurM is enhanced by this phospholipid and inhibited by its direct precursor phosphatidylglycerol. The spatial association of pneumococcal membrane phospholipids and their impact on MurM activity may therefore be critical to the final architecture of peptidoglycan and the expression of clinically relevant penicillin resistance in this pathogen.
Structure-based modeling and dynamics of MurM, a Streptococcus pneumoniae penicillin resistance determinant present at the cytoplasmic membrane.,York A, Lloyd AJ, Del Genio CI, Shearer J, Hinxman KJ, Fritz K, Fulop V, Dowson CG, Khalid S, Roper DI Structure. 2021 Jul 1;29(7):731-742.e6. doi: 10.1016/j.str.2021.03.001. Epub 2021, Mar 18. PMID:33740396[1]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
References
- ↑ York A, Lloyd AJ, Del Genio CI, Shearer J, Hinxman KJ, Fritz K, Fulop V, Dowson CG, Khalid S, Roper DI. Structure-based modeling and dynamics of MurM, a Streptococcus pneumoniae penicillin resistance determinant present at the cytoplasmic membrane. Structure. 2021 Jul 1;29(7):731-742.e6. doi: 10.1016/j.str.2021.03.001. Epub 2021, Mar 18. PMID:33740396 doi:http://dx.doi.org/10.1016/j.str.2021.03.001
