Mur ligase

From Proteopedia

Structure of MurD ligase complex with UMA, ADP and Mn+2 ion (purple) (PDB entry 3uag) Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image Function Mur ligase are a set of four Mur ubiquitin ligase enzymes: MurC, MurD, MurE, MurF which catalyze the addition of a short polypeptide to UDP-D-acetylmuramic acid in the process of bacterial cell wall buildup from peptidoglycans[1]. All four enzymes are topologically similar. MurC ligase or UDP-N-acetylmuramoyl-L-alanine ligase adds L-alanine to peptidoglycans[2]. MurD ligase or UDP-N-acetylmuramoyl-L-alanine:D-glutamate ligase catalyzes the conversion of UDP-N-acetylmuramoyl-L-alanine (UMA), D-glutamate and ATP to UDP-N-acetylmuramoyl-L-alanine-D-glutamate and ADP. I.e. adds D-glutamate to peptidoglycans[3]. MurE ligase or UDP-N-acetylmuramoyl-L-alaninyl-D-glutamate-2,6-diaminopimelate ligase adds meso-diaminpimelate to peptidoglycans[4]. MurF ligase or UDP-N-acetylmuramoyl-L-alanine-D-glutamyl-lysine-D-alanyl-D-alanine ligase adds D-alanyl-D-alanine to peptidoglycans[5]. Relevance Mur ligases are antibacterial drug targets[6]. Structural highlights . . . C-terminal domain binds the incorporated amino acid[7]. Water molecules are shown as red spheres. ,

3D Structures of Mur ligase

Updated on 10-November-2021

References

1. ↑ Munshi T, Gupta A, Evangelopoulos D, Guzman JD, Gibbons S, Keep NH, Bhakta S. Characterisation of ATP-dependent Mur ligases involved in the biogenesis of cell wall peptidoglycan in Mycobacterium tuberculosis. PLoS One. 2013;8(3):e60143. doi: 10.1371/journal.pone.0060143. Epub 2013 Mar 21. PMID:23555903 doi:http://dx.doi.org/10.1371/journal.pone.0060143
2. ↑ Deva T, Baker EN, Squire CJ, Smith CA. Structure of Escherichia coli UDP-N-acetylmuramoyl:L-alanine ligase (MurC). Acta Crystallogr D Biol Crystallogr. 2006 Dec;62(Pt 12):1466-74. Epub 2006, Nov 23. PMID:17139082 doi:10.1107/S0907444906038376
3. ↑ Perdih A, Hodoscek M, Solmajer T. MurD ligase from E. coli: Tetrahedral intermediate formation study by hybrid quantum mechanical/molecular mechanical replica path method. Proteins. 2009 Feb 15;74(3):744-59. doi: 10.1002/prot.22188. PMID:18704940 doi:http://dx.doi.org/10.1002/prot.22188
4. ↑ . PMID:212153518
5. ↑ Hrast M, Turk S, Sosic I, Knez D, Randall CP, Barreteau H, Contreras-Martel C, Dessen A, O'Neill AJ, Mengin-Lecreulx D, Blanot D, Gobec S. Structure-activity relationships of new cyanothiophene inhibitors of the essential peptidoglycan biosynthesis enzyme MurF. Eur J Med Chem. 2013 May 21;66C:32-45. doi: 10.1016/j.ejmech.2013.05.013. PMID:23786712 doi:10.1016/j.ejmech.2013.05.013
6. ↑ Kouidmi I, Levesque RC, Paradis-Bleau C. The biology of Mur ligases as an antibacterial target. Mol Microbiol. 2014 Oct;94(2):242-53. doi: 10.1111/mmi.12758. Epub 2014 Sep 5. PMID:25130693 doi:http://dx.doi.org/10.1111/mmi.12758
7. ↑ Bertrand JA, Auger G, Martin L, Fanchon E, Blanot D, Le Beller D, van Heijenoort J, Dideberg O. Determination of the MurD mechanism through crystallographic analysis of enzyme complexes. J Mol Biol. 1999 Jun 11;289(3):579-90. PMID:10356330 doi:10.1006/jmbi.1999.2800