4c13

x-ray crystal structure of Staphylococcus aureus MurE with UDP-MurNAc- Ala-Glu-Lys

spinqualitylabelsall models 4c13, resolution 1.90Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 4c13 is a 1 chain structure with sequence from "micrococcus_aureus"_(rosenbach_1884)_zopf_1885 "micrococcus aureus" (rosenbach 1884) zopf 1885. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance. Ligands: CL, K, MG, PO4, UML NonStd Res: KCX Related: 4c12 Activity: UDP-N-acetylmuramoyl-L-alanyl-D-glutamate--L-lysine ligase, with EC number 6.3.2.7 Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT Function [D4U2M7_STAAU] Catalyzes the addition of L-lysine to the nucleotide precursor UDP-N-acetylmuramoyl-L-alanyl-D-glutamate (UMAG) in the biosynthesis of bacterial cell-wall peptidoglycan (By similarity).[HAMAP-Rule:MF_00208] Publication Abstract from PubMed Formation of the peptidoglycan stem pentapeptide requires the insertion of both L or D amino acids by the ATP dependent ligase enzymes MurC, D, E and F. The stereo chemical control of the third position amino acid in the pentapeptide, is crucial to maintain the fidelity of later biosynthetic steps contributing to cell morphology, antibiotic resistance and pathogenesis. Here we determine the X-ray crystal structure of Staphylococcus aureus MurE UDP-N-acetylmuramoyl-l-alanyl-d-glutamate: meso-2,6-diaminopimelate ligase (MurE) (E.C. 6.3.2.15) at 1.8 angstrom resolution in the presence of ADP and the reaction product, UDP-MurNAc-L-Ala-gamma-D-Glu-L-Lys. This structure provides for the first time a molecular understanding of how this Gram-positive enzyme discriminates between L-lysine and D,L-diaminopimelic acid, the predominant amino acid that replaces L-lysine in Gram-negative peptidoglycan. Despite the presence of a consensus sequence previously implicated in the selection of the third position residue in the stem pentapeptide in S. aureus MurE, the structure shows that only part of this sequence is involved in the selection of L-lysine. Instead, other parts of the protein contribute substrate-selecting residues resulting in a lysine-binding pocket based on charge characteristics. Despite the absolute specificity for L-lysine, S. aureus MurE binds this substrate relatively poorly. In-vivo analysis and metabolomic data reveals that this is compensated for by high cytoplasmic L-lysine concentrations. Therefore both metabolic and structural constraints maintain the structural integrity of the staphylococcal peptidoglycan. This study provides a novel focus for S. aureus directed antimicrobials based, on dual targeting of essential amino acid biogenesis and its linkage to cell wall assembly. Specificity Determinants for Lysine Incorporation in Staphylococcus aureus Peptidoglycan as Revealed by the Structure of a MurE Ternary Complex.,Ruane KM, Lloyd AJ, Fulop V, Dowson CG, Barreteau H, Boniface A, Dementin S, Blanot D, Mengin-Lecreulx D, Gobec S, Dessen A, Roper DI J Biol Chem. 2013 Sep 24. PMID:24064214 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

Proteopedia Page Contributors and Editors (what is this?)

OCA