Enzymes
UniProtKB help_outline | 7,915 proteins |
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- Name help_outline β-D-GlcNAc-(1→4)-Mur2Ac(oyl-L-Ala-γ-D-O-P-Glu-L-Lys-D-Ala-D-Ala)-di-trans,octa-cis-undecaprenyl diphosphate Identifier CHEBI:143132 Charge -4 Formula C94H153N8O29P3 InChIKeyhelp_outline YVDOHCYUJLXIMH-OVTFQNCVSA-J SMILEShelp_outline CC(=CCC/C(=C/CC/C(=C/CC\C(\C)=C/CC\C(\C)=C/CC\C(\C)=C/CC/C(=C\CC\C(\C)=C/CC\C(\C)=C/CC\C(\C)=C/CC\C(\C)=C/COP(=O)([O-])OP(O[C@@H]1[C@@H]([C@H]([C@@H]([C@H](O1)CO)O[C@@H]2O[C@@H]([C@H]([C@@H]([C@H]2NC(=O)C)O)O)CO)O[C@@H](C(=O)N[C@H](C(N[C@@H](C(=O)OP(=O)([O-])[O-])CCC(N[C@H](C(N[C@@H](C(N[C@@H](C([O-])=O)C)=O)C)=O)CCCC[NH3+])=O)=O)C)C)NC(C)=O)(=O)[O-])/C)/C)/C)C 2D coordinates Mol file for the small molecule Search links Involved in 2 reaction(s) Find molecules that contain or resemble this structure Find proteins in UniProtKB for this molecule
- Name help_outline NH4+ Identifier CHEBI:28938 (CAS: 14798-03-9) help_outline Charge 1 Formula H4N InChIKeyhelp_outline QGZKDVFQNNGYKY-UHFFFAOYSA-O SMILEShelp_outline [H][N+]([H])([H])[H] 2D coordinates Mol file for the small molecule Search links Involved in 527 reaction(s) Find molecules that contain or resemble this structure Find proteins in UniProtKB for this molecule
- Name help_outline β-D-GlcNAc-(1→4)-Mur2Ac(oyl-L-Ala-D-isoglutaminyl-L-Lys-D-Ala-D-Ala)-di-trans,octa-cis-undecaprenyl diphosphate Identifier CHEBI:62233 Charge -2 Formula C94H155N9O25P2 InChIKeyhelp_outline CALJPWOWZPDIQK-PRHZHQPTSA-L SMILEShelp_outline C[C@@H](NC(=O)[C@@H](C)NC(=O)[C@H](CCCC[NH3+])NC(=O)CC[C@@H](NC(=O)[C@H](C)NC(=O)[C@@H](C)O[C@@H]1[C@@H](NC(C)=O)[C@H](O[C@H](CO)[C@H]1O[C@@H]1O[C@H](CO)[C@@H](O)[C@H](O)[C@H]1NC(C)=O)OP([O-])(=O)OP([O-])(=O)OC\C=C(\C)CC\C=C(\C)CC\C=C(\C)CC\C=C(\C)CC\C=C(\C)CC\C=C(\C)CC\C=C(\C)CC\C=C(\C)CC\C=C(/C)CC\C=C(/C)CCC=C(C)C)C(N)=O)C([O-])=O 2D coordinates Mol file for the small molecule Search links Involved in 3 reaction(s) Find molecules that contain or resemble this structure Find proteins in UniProtKB for this molecule
- Name help_outline H+ Identifier CHEBI:15378 Charge 1 Formula H InChIKeyhelp_outline GPRLSGONYQIRFK-UHFFFAOYSA-N SMILEShelp_outline [H+] 2D coordinates Mol file for the small molecule Search links Involved in 9,331 reaction(s) Find molecules that contain or resemble this structure Find proteins in UniProtKB for this molecule
- Name help_outline phosphate Identifier CHEBI:43474 Charge -2 Formula HO4P InChIKeyhelp_outline NBIIXXVUZAFLBC-UHFFFAOYSA-L SMILEShelp_outline OP([O-])([O-])=O 2D coordinates Mol file for the small molecule Search links Involved in 992 reaction(s) Find molecules that contain or resemble this structure Find proteins in UniProtKB for this molecule
Cross-references
RHEA:57932 | RHEA:57933 | RHEA:57934 | RHEA:57935 | |
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Reaction direction help_outline | undefined | left-to-right | right-to-left | bidirectional |
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Publications
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Identification and in vitro analysis of the GatD/MurT enzyme-complex catalyzing lipid II amidation in Staphylococcus aureus.
Muench D., Roemer T., Lee S.H., Engeser M., Sahl H.G., Schneider T.
The peptidoglycan of Staphylococcus aureus is characterized by a high degree of crosslinking and almost completely lacks free carboxyl groups, due to amidation of the D-glutamic acid in the stem peptide. Amidation of peptidoglycan has been proposed to play a decisive role in polymerization of cell ... >> More
The peptidoglycan of Staphylococcus aureus is characterized by a high degree of crosslinking and almost completely lacks free carboxyl groups, due to amidation of the D-glutamic acid in the stem peptide. Amidation of peptidoglycan has been proposed to play a decisive role in polymerization of cell wall building blocks, correlating with the crosslinking of neighboring peptidoglycan stem peptides. Mutants with a reduced degree of amidation are less viable and show increased susceptibility to methicillin. We identified the enzymes catalyzing the formation of D-glutamine in position 2 of the stem peptide. We provide biochemical evidence that the reaction is catalyzed by a glutamine amidotransferase-like protein and a Mur ligase homologue, encoded by SA1707 and SA1708, respectively. Both proteins, for which we propose the designation GatD and MurT, are required for amidation and appear to form a physically stable bi-enzyme complex. To investigate the reaction in vitro we purified recombinant GatD and MurT His-tag fusion proteins and their potential substrates, i.e. UDP-MurNAc-pentapeptide, as well as the membrane-bound cell wall precursors lipid I, lipid II and lipid II-Gly₅. In vitro amidation occurred with all bactoprenol-bound intermediates, suggesting that in vivo lipid II and/or lipid II-Gly₅ may be substrates for GatD/MurT. Inactivation of the GatD active site abolished lipid II amidation. Both, murT and gatD are organized in an operon and are essential genes of S. aureus. BLAST analysis revealed the presence of homologous transcriptional units in a number of gram-positive pathogens, e.g. Mycobacterium tuberculosis, Streptococcus pneumonia and Clostridium perfringens, all known to have a D-iso-glutamine containing PG. A less negatively charged PG reduces susceptibility towards defensins and may play a general role in innate immune signaling. << Less
PLoS Pathog. 8:E1002509-E1002509(2012) [PubMed] [EuropePMC]
This publication is cited by 2 other entries.
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Structural basis of cell wall peptidoglycan amidation by the GatD/MurT complex of Staphylococcus aureus.
Noldeke E.R., Muckenfuss L.M., Niemann V., Muller A., Stork E., Zocher G., Schneider T., Stehle T.
The peptidoglycan of Staphylococcus aureus is highly amidated. Amidation of α-D-isoglutamic acid in position 2 of the stem peptide plays a decisive role in the polymerization of cell wall building blocks. S. aureus mutants with a reduced degree of amidation are less viable and show increased susce ... >> More
The peptidoglycan of Staphylococcus aureus is highly amidated. Amidation of α-D-isoglutamic acid in position 2 of the stem peptide plays a decisive role in the polymerization of cell wall building blocks. S. aureus mutants with a reduced degree of amidation are less viable and show increased susceptibility to methicillin, indicating that targeting the amidation reaction could be a useful strategy to combat this pathogen. The enzyme complex that catalyzes the formation of α-D-isoglutamine in the Lipid II stem peptide was identified recently and shown to consist of two subunits, the glutamine amidotransferase-like protein GatD and the Mur ligase homolog MurT. We have solved the crystal structure of the GatD/MurT complex at high resolution, revealing an open, boomerang-shaped conformation in which GatD is docked onto one end of MurT. Putative active site residues cluster at the interface between GatD and MurT and are contributed by both proteins, thus explaining the requirement for the assembled complex to carry out the reaction. Site-directed mutagenesis experiments confirm the validity of the observed interactions. Small-angle X-ray scattering data show that the complex has a similar conformation in solution, although some movement at domain interfaces can occur, allowing the two proteins to approach each other during catalysis. Several other Gram-positive pathogens, including Streptococcus pneumoniae, Clostridium perfringens and Mycobacterium tuberculosis have homologous enzyme complexes. Combined with established biochemical assays, the structure of the GatD/MurT complex provides a solid basis for inhibitor screening in S. aureus and other pathogens. << Less
Sci. Rep. 8:12953-12953(2018) [PubMed] [EuropePMC]
This publication is cited by 2 other entries.
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Structure of the essential peptidoglycan amidotransferase MurT/GatD complex from Streptococcus pneumoniae.
Morlot C., Straume D., Peters K., Hegnar O.A., Simon N., Villard A.M., Contreras-Martel C., Leisico F., Breukink E., Gravier-Pelletier C., Le Corre L., Vollmer W., Pietrancosta N., Havarstein L.S., Zapun A.
The universality of peptidoglycan in bacteria underlies the broad spectrum of many successful antibiotics. However, in our times of widespread resistance, the diversity of peptidoglycan modifications offers a variety of new antibacterials targets. In some Gram-positive species such as Streptococcu ... >> More
The universality of peptidoglycan in bacteria underlies the broad spectrum of many successful antibiotics. However, in our times of widespread resistance, the diversity of peptidoglycan modifications offers a variety of new antibacterials targets. In some Gram-positive species such as Streptococcus pneumoniae, Staphylococcus aureus, or Mycobacterium tuberculosis, the second residue of the peptidoglycan precursor, D-glutamate, is amidated into iso-D-glutamine by the essential amidotransferase MurT/GatD complex. Here, we present the structure of this complex at 3.0 Å resolution. MurT has central and C-terminal domains similar to Mur ligases with a cysteine-rich insertion, which probably binds zinc, contributing to the interface with GatD. The mechanism of amidation by MurT is likely similar to the condensation catalyzed by Mur ligases. GatD is a glutaminase providing ammonia that is likely channeled to the MurT active site through a cavity network. The structure and assay presented here constitute a knowledge base for future drug development studies. << Less
Nat. Commun. 9:3180-3180(2018) [PubMed] [EuropePMC]
This publication is cited by 2 other entries.
Comments
RHEA:57932 part of RHEA:57928