9ls8 | pdb_00009ls8

Crystal structure of peptidyl-tRNA hydrolase from Enterococcus faecium at 1.22 A

spinqualitylabelsall models 9ls8, resolution 1.22Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 9ls8 is a 1 chain structure with sequence from Enterococcus faecium. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance. Method: X-ray diffraction, Resolution 1.22Å Ligands: BME, EDO, NA, SO4 Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT Function A0A133CPV0_ENTFC The natural substrate for this enzyme may be peptidyl-tRNAs which drop off the ribosome during protein synthesis.[HAMAP-Rule:MF_00083] Publication Abstract from PubMed In bacteria, peptidyl-tRNA hydrolase (Pth, E.C. 3.1.1.29) is a ubiquitous and essential enzyme for preventing the accumulation of peptidyl-tRNA and sequestration of tRNA. Pth is an esterase that cleaves the ester bond between peptide and tRNA. Here, we present the crystal structure of Pth from Enterococcus faecium (EfPth) at a resolution of 1.92 A. The two molecules in the asymmetric unit differ in the orientation of sidechain of N66, a conserved residue of the catalytic site. Enzymatic hydrolysis of substrate alpha-N-BODIPY-lysyl-tRNA(Lys) (BLT) by EfPth was characterized by Michaelis-Menten parameters K(M) 163.5 nM and Vmax 1.9 nM/s. Compounds having pyrrolinone scaffold were tested for inhibition of Pth and one compound, 1040-C, was found to have IC(50) of 180 nM. Antimicrobial activity profiling was done for 1040-C. It exhibited equipotent activity against drug-susceptible and resistant S. aureus (MRSA and VRSA) and Enterococcus (VSE and VRE) with MICs 2-8 mug/mL. 1040-C synergized with gentamicin and the combination was effective against the gentamicin resistant S. aureus strain NRS-119. 1040-C was found to reduce biofilm mass of S. aureus to an extent similar to Vancomycin. In a murine model of infection, 1040-C was able to reduce bacterial load to an extent comparable to Vancomycin. Characterization of structure of peptidyl-tRNA hydrolase from Enterococcus faecium and its inhibition by a pyrrolinone compound.,Pandey R, Kaul G, Akhir A, Saxena D, Shukla M, Mundra S, Zohib M, Singh S, Pal RK, Tripathi S, Jain A, Chopra S, Arora A Int J Biol Macromol. 2024 Jun 28;275(Pt 1):133445. doi: , 10.1016/j.ijbiomac.2024.133445. PMID:38945334 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

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