FunctionMur 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].
RelevanceMur ligases are antibacterial drug targets[6].
Structural highlights.
- .
- . C-terminal domain binds the incorporated amino acid[7]. Water molecules are shown as red spheres.
- ,
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3D Structures of Mur ligase3D Structures of Mur ligase
Updated on 10-November-2021
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- MurD or UDP-N-acetylmuramic acid L-alanyl-D-glutmate ligase
- 1e0d, 5a5e – EcMurD – Escherichia coli
- 3lk7 – MurD – Streptococcus agalactiae
- 4buc – TmMurD – Thermotoga maritima
- MurD complex with ligand
- 1uag, 1eeh – EcMurD + UMA
- 2jfg – EcMurD + UMA + ADP
- 2uag – EcMurD + UMA + ADP + Mg
- 3uag – EcMurD + UMA + ADP + Mn
- 5a5f – EcMurD + UMA + ADP + malonate
- 4uag – EcMurD + UAG
- 4bub – TmMurD + ADP
- MurD complex with inhibitor
- 2jff, 2jfh, 2uuo, 2uup, 2vtd, 2vte, 2xpc – EcMurD + sulfonamide inhibitor
- 2wjp – EcMurD + rhodanine inhibitor
- 2x5o, 2y68, 2y66, 2y67, 2y1o – EcMurD + thiazolidine inhibitor
- MurC or UDP-N-acetylmuramic acid L-alanine ligase
- 1j6u – TmMurC
- 7bva – MtMurC – Mycobacterium tuberculosis
- 7bvb – MtMurC + UAG
- 6cau – AbMurC + AMPPNP – Acinetobacter baumannii
- 6x9f, 6x9n – MurC + inhibitor – Pseudomonas aeruginosa
- 6vr7 – MfMurC – Methanothermus fervidus
- MurE or UDP-N-acetylmuramic acid L-alanyl-D-glutmate-2,6-diaminopimelate ligase
- 2xja – MtMurE + dipeptide + ADP – Mycobacterium tuberculosis
- 2wtz – MtMurE + UAG
- 7b53 – EcMurE
- 7b6o – EcMurE (mutant)
- 1e8c – EcMurE + UDP-tripeptide + UAG
- 7b60, 7b61, 7b68, 7b6g, 7b6i, 7b6j, 7b6l, 7b6k, 7b6m, 7b6n, 7b6q, 7b9e, 7b9w – EcMurE + inhibitor
- 7b6p – EcMurE (mutant) + inhibitor
- 4c12 – SaMurE + UML + ADP – Staphylococcus aureus
- 4c13 – SaMurE + UML
- 7jt8 – MfMurE
- 6vr8 – MfMurE + UDP
- 7d27, 7sir – AbMurE
- MurF
- 3ddt – hMurF-1 ZF-B box + Zn – human
- 2d8u – hMurF-1 ZF-B box + Zn - NMR
- 3q1d – hMurF-3
- 4m3l – hMurF-1 coiled coil domain
- 2am1, 2am2, 3zm5, 3zm6 – SpMurF + inhibitor – Streptococcus pneumoniae
- 3zl8 – TmMurF + ADP
- 1gg4 – EcMurF
- 4qdi, 4qf5, 4ziy – MurF - Acinetobacter baumannii
- 4cvl – PaMurF + AMPPNP - Pseudomonas aeruginosa
- 4cvk – PaMurF + UDP-MurNac
- 4cvm – PaMurF + UDP-MurNac + AMPPNP
- MurT
- 6fqb – SpMurT + glutamine amidotransferase
- 6gs2 – SaMurT + glutamine amidotransferase
- 6h5e – SaMurT + glutamine amidotransferase + AMPPNP
ReferencesReferences
- ↑ 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
- ↑ 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
- ↑ 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
- ↑ . PMID:212153518
- ↑ 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
- ↑ 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
- ↑ 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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