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

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  • .
  • . C-terminal domain binds the incorporated amino acid[7]. Water molecules are shown as red spheres.
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Structure of MurD ligase complex with UMA, ADP and Mn+2 ion (purple) (PDB entry 3uag)

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3D Structures of Mur ligase3D Structures of Mur ligase

Updated on 10-November-2021

ReferencesReferences

  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

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