6gs2: Difference between revisions
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The | ==Crystal Structure of the GatD/MurT Enzyme Complex from Staphylococcus aureus== | ||
<StructureSection load='6gs2' size='340' side='right' caption='[[6gs2]], [[Resolution|resolution]] 2.04Å' scene=''> | |||
== Structural highlights == | |||
<table><tr><td colspan='2'>[[6gs2]] is a 4 chain structure with sequence from [http://en.wikipedia.org/wiki/Staan Staan]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6GS2 OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=6GS2 FirstGlance]. <br> | |||
</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=144:TRIS-HYDROXYMETHYL-METHYL-AMMONIUM'>144</scene>, <scene name='pdbligand=MG:MAGNESIUM+ION'>MG</scene>, <scene name='pdbligand=PEG:DI(HYDROXYETHYL)ETHER'>PEG</scene>, <scene name='pdbligand=ZN:ZINC+ION'>ZN</scene></td></tr> | |||
<tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">SA1707 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=158879 STAAN]), SA1708 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=158879 STAAN])</td></tr> | |||
<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=6gs2 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6gs2 OCA], [http://pdbe.org/6gs2 PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=6gs2 RCSB], [http://www.ebi.ac.uk/pdbsum/6gs2 PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=6gs2 ProSAT]</span></td></tr> | |||
</table> | |||
<div style="background-color:#fffaf0;"> | |||
== Publication Abstract from PubMed == | |||
The peptidoglycan of Staphylococcus aureus is highly amidated. Amidation of alpha-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 alpha-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. | |||
Structural basis of cell wall peptidoglycan amidation by the GatD/MurT complex of Staphylococcus aureus.,Noldeke ER, Muckenfuss LM, Niemann V, Muller A, Stork E, Zocher G, Schneider T, Stehle T Sci Rep. 2018 Aug 28;8(1):12953. doi: 10.1038/s41598-018-31098-x. PMID:30154570<ref>PMID:30154570</ref> | |||
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | |||
[[Category: | </div> | ||
<div class="pdbe-citations 6gs2" style="background-color:#fffaf0;"></div> | |||
== References == | |||
<references/> | |||
__TOC__ | |||
</StructureSection> | |||
[[Category: Staan]] | |||
[[Category: Muckenfuss, L M]] | |||
[[Category: Niemann, V]] | |||
[[Category: Noeldeke, E R]] | |||
[[Category: Stehle, T]] | |||
[[Category: Zocher, G]] | |||
[[Category: Antibiotic resistance]] | |||
[[Category: Biosynthetic protein]] | |||
[[Category: Cell wall biosynthesis]] | |||
[[Category: Peptidoglycan]] | |||
Latest revision as of 10:55, 12 September 2018
Crystal Structure of the GatD/MurT Enzyme Complex from Staphylococcus aureusCrystal Structure of the GatD/MurT Enzyme Complex from Staphylococcus aureus
Structural highlights
Publication Abstract from PubMedThe peptidoglycan of Staphylococcus aureus is highly amidated. Amidation of alpha-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 alpha-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. Structural basis of cell wall peptidoglycan amidation by the GatD/MurT complex of Staphylococcus aureus.,Noldeke ER, Muckenfuss LM, Niemann V, Muller A, Stork E, Zocher G, Schneider T, Stehle T Sci Rep. 2018 Aug 28;8(1):12953. doi: 10.1038/s41598-018-31098-x. PMID:30154570[1] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. References
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