9wqx: Difference between revisions
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==aminoacyl-tRNA-dependent peptide synthase, Sbb17, complexed with streptothrisamine== | |||
<StructureSection load='9wqx' size='340' side='right'caption='[[9wqx]], [[Resolution|resolution]] 2.50Å' scene=''> | |||
== Structural highlights == | |||
<table><tr><td colspan='2'>[[9wqx]] is a 1 chain structure with sequence from [https://en.wikipedia.org/wiki/Streptomyces Streptomyces]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=9WQX OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=9WQX FirstGlance]. <br> | |||
</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 2.5Å</td></tr> | |||
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=A1L3W:[(2~{R},3~{R},4~{S},5~{R},6~{R})-6-[(~{Z})-[(3~{a}~{S},7~{R},7~{a}~{S})-7-oxidanyl-4-oxidanylidene-3,3~{a},5,6,7,7~{a}-hexahydro-1~{H}-imidazo[4,5-c]pyridin-2-ylidene]amino]-5-azanyl-2-(hydroxymethyl)-4-oxidanyl-oxan-3-yl]+carbamate'>A1L3W</scene></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=9wqx FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=9wqx OCA], [https://pdbe.org/9wqx PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=9wqx RCSB], [https://www.ebi.ac.uk/pdbsum/9wqx PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=9wqx ProSAT]</span></td></tr> | |||
</table> | |||
<div style="background-color:#fffaf0;"> | |||
== Publication Abstract from PubMed == | |||
Streptothricin (ST) antibiotics are promising agents against multidrug-resistant pathogens and are structurally classified into two groups, containing either a beta-lysyl or a glycyl pendant moiety attached via an amide bond to an amino sugar core. These pendant moieties are essential determinants of the biological activity and selective toxicity of ST antibiotics. We previously demonstrated that during ST biosynthesis, the beta-lysyl pendant moiety is installed by nonribosomal peptide synthetases, whereas the glycyl pendant moiety is generated by a Gly-tRNA(Gly)-dependent amide-forming enzyme. Here, we present a chemoenzymatic approach to transform aminoacyl pendant moieties using the promiscuous tRNA-dependent amide-forming enzyme Sba18. Remarkably, Sba18 generates two new ST derivatives, alanylthricin and serylthricin, by utilizing Ala-tRNA(Ala) and Ser-tRNA(Ser), respectively. Moreover, Sba18 accepts aminoacyl-tRNA mimics prepared by flexizyme-mediated charging of chemically synthesized aminoacyl groups and produces additional 11 ST derivatives. Alanylthricin and serylthricin retain antibiotic activity, demonstrating that this tRNA-dependent chemoenzymatic approach provides a viable strategy for expanding the structural diversity of streptothricin antibiotics. Furthermore, structural comparison of Sba18 with its Gly-tRNA(Gly)-specific orthologue Sbb17 elucidates the catalytic and substrate-recognition mechanisms underlying the broad specificity of Sba18. These structural insights provide a foundation for expanding the structural diversity not only of ST antibiotics but also of other peptide natural products biosynthesized using aminoacyl-tRNAs. | |||
tRNA-Dependent Chemoenzymatic Transformation of Aminoacyl Pendant Moieties of Streptothricin Antibiotics.,Maruyama C, Nakashima Y, Matsuda K, A Hamdy S, Uchiyama S, Goto Y, Mori T, Ogasawara Y, Shin-Ya K, Abe I, Dairi T, Suga H, Morita H, Hamano Y J Am Chem Soc. 2026 Mar 25;148(11):12154-12165. doi: 10.1021/jacs.6c00367. Epub , 2026 Mar 13. PMID:41823201<ref>PMID:41823201</ref> | |||
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | |||
[[Category: | </div> | ||
<div class="pdbe-citations 9wqx" style="background-color:#fffaf0;"></div> | |||
== References == | |||
<references/> | |||
__TOC__ | |||
</StructureSection> | |||
[[Category: Large Structures]] | |||
[[Category: Streptomyces]] | |||
[[Category: Hamano Y]] | |||
[[Category: Maruyama C]] | |||
[[Category: Morita H]] | |||
[[Category: Nakashima Y]] | |||
[[Category: Sherif HAMA]] | |||