7wpt

Methionyl-tRNA synthetase from Staphylococcus aureus complexed with a fragment M2-80 and ATP

spinqualitylabelsall models 7wpt, resolution 2.26Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 7wpt is a 1 chain structure with sequence from Staphylococcus aureus subsp. aureus COL. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance. Method: X-ray diffraction, Resolution 2.26Å Ligands: ATP, EDO, GOL, XM0 Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT Function SYM_STAAC Is required not only for elongation of protein synthesis but also for the initiation of all mRNA translation through initiator tRNA(fMet) aminoacylation. Publication Abstract from PubMed Methionyl-tRNA synthetase (MetRS) charges tRNAMet with l-methionine (L-Met) to decode the ATG codon for protein translation, making it indispensable for all cellular lives. Many gram-positive bacteria use a type 1 MetRS (MetRS1), which is considered a promising antimicrobial drug target due to its low sequence identity with human cytosolic MetRS (HcMetRS, which belongs to MetRS2). Here, we report crystal structures of a representative MetRS1 from Staphylococcus aureus (SaMetRS) in its apo and substrate-binding forms. The connecting peptide (CP) domain of SaMetRS differs from HcMetRS in structural organization and dynamic movement. We screened 1049 chemical fragments against SaMetRS preincubated with or without substrate ATP, and ten hits were identified. Four cocrystal structures revealed that the fragments bound to either the L-Met binding site or an auxiliary pocket near the tRNA CCA end binding site of SaMetRS. Interestingly, fragment binding was enhanced by ATP in most cases, suggesting a potential ATP-assisted ligand binding mechanism in MetRS1. Moreover, co-binding with ATP was also observed in our cocrystal structure of SaMetRS with a class of newly reported inhibitors that simultaneously occupied the auxiliary pocket, tRNA site and L-Met site. Our findings will inspire the development of new MetRS1 inhibitors for fighting microbial infections. Fragment screening and structural analyses highlight the ATP-assisted ligand binding for inhibitor discovery against type 1 methionyl-tRNA synthetase.,Yi J, Cai Z, Qiu H, Lu F, Luo Z, Chen B, Gu Q, Xu J, Zhou H Nucleic Acids Res. 2022 Apr 26. pii: 6574669. doi: 10.1093/nar/gkac285. PMID:35474479 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See Also Aminoacyl tRNA synthetase 3D structures

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