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Line 59: |
| *MurF | | *MurF |
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| **[[2am1]], [[2am2]], [[3zm5]], [[3zm6]] – MurF + inhibitor – ''Streptococcus pneumoniae''<br />
| |
| **[[3zl8]] – TmMurF + ADP <br />
| |
| **[[1gg4]] – EcMurF <br />
| |
| **[[3ddt]] – hMurF-1 ZF-B box + Zn – human <br /> | | **[[3ddt]] – hMurF-1 ZF-B box + Zn – human <br /> |
| **[[2d8u]] – hMurF-1 ZF-B box + Zn - NMR<br /> | | **[[2d8u]] – hMurF-1 ZF-B box + Zn - NMR<br /> |
| **[[3q1d]] – hMurF-3<br /> | | **[[3q1d]] – hMurF-3<br /> |
| **[[4m3l]] – hMurF-1 coiled coil domain<br /> | | **[[4m3l]] – hMurF-1 coiled coil domain<br /> |
| | **[[2am1]], [[2am2]], [[3zm5]], [[3zm6]] – SpMurF + inhibitor – ''Streptococcus pneumoniae''<br /> |
| | **[[3zl8]] – TmMurF + ADP <br /> |
| | **[[1gg4]] – EcMurF <br /> |
| **[[4qdi]], [[4qf5]], [[4ziy]] – MurF - ''Acinetobacter baumannii'' <br /> | | **[[4qdi]], [[4qf5]], [[4ziy]] – MurF - ''Acinetobacter baumannii'' <br /> |
| **[[4cvl]] – PaMurF + AMPPNP - ''Pseudomonas aeruginosa''<br /> | | **[[4cvl]] – PaMurF + AMPPNP - ''Pseudomonas aeruginosa''<br /> |
| **[[4cvk]] – PaMurF + UDP-MurNac<br /> | | **[[4cvk]] – PaMurF + UDP-MurNac<br /> |
| **[[4cvm]] – PaMurF + UDP-MurNac + AMPPNP<br /> | | **[[4cvm]] – PaMurF + UDP-MurNac + AMPPNP<br /> |
| | |
| | *MurT |
| | |
| | **[[6fqb]] – SpMurT + glutamine amidotransferase <br /> |
| }} | | }} |
| == References == | | == References == |
| <references/> | | <references/> |
| [[Category:Topic Page]] | | [[Category:Topic Page]] |
| 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
MurD contains three domains.
- ↑ 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:https://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:https://dx.doi.org/10.1002/prot.22188
- ↑ PMID: https://pubmed.ncbi.nlm.nih.gov/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:https://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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3D Structures of Mur ligase
Updated on 08-September-2020
{"openlevels":0}
- MurD
- 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
- MurE
- 2xja – MtMurE + dipeptide + ADP – Mycobacterium tuberculosis
- 2wtz – MtMurE + UAG
- 1e8c – EcMurE + UDP-tripeptide + UAG
- 4c12 – SaMurE + UML + ADP – Staphylococcus aureus
- 4c13 – SaMurE + UML
- 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
References