7wpj: Difference between revisions
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==Methionyl-tRNA synthetase from Staphylococcus aureus== | ==Methionyl-tRNA synthetase from Staphylococcus aureus== | ||
<StructureSection load='7wpj' size='340' side='right'caption='[[7wpj]]' scene=''> | <StructureSection load='7wpj' size='340' side='right'caption='[[7wpj]], [[Resolution|resolution]] 2.65Å' scene=''> | ||
== Structural highlights == | == Structural highlights == | ||
<table><tr><td colspan='2'>Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=7WPJ OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=7WPJ FirstGlance]. <br> | <table><tr><td colspan='2'>[[7wpj]] is a 1 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=7WPJ OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=7WPJ FirstGlance]. <br> | ||
</td></tr><tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=7wpj FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7wpj OCA], [https://pdbe.org/7wpj PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=7wpj RCSB], [https://www.ebi.ac.uk/pdbsum/7wpj PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=7wpj ProSAT]</span></td></tr> | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=EDO:1,2-ETHANEDIOL'>EDO</scene></td></tr> | ||
<tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[https://en.wikipedia.org/wiki/Methionine--tRNA_ligase Methionine--tRNA ligase], with EC number [https://www.brenda-enzymes.info/php/result_flat.php4?ecno=6.1.1.10 6.1.1.10] </span></td></tr> | |||
<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=7wpj FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7wpj OCA], [https://pdbe.org/7wpj PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=7wpj RCSB], [https://www.ebi.ac.uk/pdbsum/7wpj PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=7wpj ProSAT]</span></td></tr> | |||
</table> | </table> | ||
== Function == | |||
[[https://www.uniprot.org/uniprot/SYM_STAAC 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. | |||
<div style="background-color:#fffaf0;"> | |||
== 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<ref>PMID:35474479</ref> | |||
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | |||
</div> | |||
<div class="pdbe-citations 7wpj" style="background-color:#fffaf0;"></div> | |||
== References == | |||
<references/> | |||
__TOC__ | __TOC__ | ||
</StructureSection> | </StructureSection> | ||
[[Category: Large Structures]] | [[Category: Large Structures]] | ||
[[Category: Cai Z]] | [[Category: Methionine--tRNA ligase]] | ||
[[Category: Chen B]] | [[Category: Cai, Z]] | ||
[[Category: Gu Q]] | [[Category: Chen, B]] | ||
[[Category: Lu F]] | [[Category: Gu, Q]] | ||
[[Category: Luo Z]] | [[Category: Lu, F]] | ||
[[Category: Qiu H]] | [[Category: Luo, Z]] | ||
[[Category: Xu J]] | [[Category: Qiu, H]] | ||
[[Category: Yi J]] | [[Category: Xu, J]] | ||
[[Category: Zhou H]] | [[Category: Yi, J]] | ||
[[Category: Zhou, H]] | |||
[[Category: Inhibitor]] | |||
[[Category: Ligase]] | |||
Revision as of 13:29, 18 May 2022
Methionyl-tRNA synthetase from Staphylococcus aureusMethionyl-tRNA synthetase from Staphylococcus aureus
Structural highlights
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 PubMedMethionyl-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[1] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. References
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