6t6x: Difference between revisions
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==Structure of the Bottromycin epimerase BotH in complex with substrate== | ==Structure of the Bottromycin epimerase BotH in complex with substrate== | ||
<StructureSection load='6t6x' size='340' side='right'caption='[[6t6x]]' scene=''> | <StructureSection load='6t6x' size='340' side='right'caption='[[6t6x]], [[Resolution|resolution]] 1.25Å' 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=6T6X OCA]. For a <b>guided tour on the structure components</b> use [ | <table><tr><td colspan='2'>[[6t6x]] is a 1 chain structure with sequence from [https://en.wikipedia.org/wiki/Streptomyces_sp._BC16019 Streptomyces sp. BC16019]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6T6X OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=6T6X FirstGlance]. <br> | ||
</td></tr><tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[ | </td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 1.25Å</td></tr> | ||
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=MQW:(4~{R})-2-[(1~{R})-1-[[(2~{S})-2-[[(2~{S})-3-methyl-2-[[(4~{Z},6~{S},9~{S},12~{S})-2,8,11-tris(oxidanylidene)-6,9-di(propan-2-yl)-1,4,7,10-tetrazabicyclo[10.3.0]pentadec-4-en-5-yl]amino]butanoyl]amino]-3-phenyl-propanoyl]amino]-3-oxidanyl-3-oxidanylidene-propyl]-4,5-dihydro-1,3-thiazole-4-carboxylic+acid'>MQW</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=6t6x FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6t6x OCA], [https://pdbe.org/6t6x PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=6t6x RCSB], [https://www.ebi.ac.uk/pdbsum/6t6x PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=6t6x ProSAT]</span></td></tr> | |||
</table> | </table> | ||
== Function == | |||
[https://www.uniprot.org/uniprot/K4MHV9_9ACTN K4MHV9_9ACTN] | |||
<div style="background-color:#fffaf0;"> | |||
== Publication Abstract from PubMed == | |||
D-amino acids endow peptides with diverse, desirable properties, but the post-translational and site-specific epimerization of L-amino acids into their D-counterparts is rare and chemically challenging. Bottromycins are ribosomally synthesized and post-translationally modified peptides that have overcome this challenge and feature a D-aspartate (D-Asp), which was proposed to arise spontaneously during biosynthesis. We have identified the highly unusual alpha/beta-hydrolase (ABH) fold enzyme BotH as a peptide epimerase responsible for the post-translational epimerization of L-Asp to D-Asp during bottromycin biosynthesis. The biochemical characterization of BotH combined with the structures of BotH and the BotH-substrate complex allowed us to propose a mechanism for this reaction. Bioinformatic analyses of BotH homologs show that similar ABH enzymes are found in diverse biosynthetic gene clusters. This places BotH as the founding member of a group of atypical ABH enzymes that may be able to epimerize non-Asp stereocenters across different families of secondary metabolites. | |||
The bottromycin epimerase BotH defines a group of atypical alpha/beta-hydrolase-fold enzymes.,Sikandar A, Franz L, Adam S, Santos-Aberturas J, Horbal L, Luzhetskyy A, Truman AW, Kalinina OV, Koehnke J Nat Chem Biol. 2020 Sep;16(9):1013-1018. doi: 10.1038/s41589-020-0569-y. Epub, 2020 Jun 29. PMID:32601484<ref>PMID:32601484</ref> | |||
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | |||
</div> | |||
<div class="pdbe-citations 6t6x" style="background-color:#fffaf0;"></div> | |||
== References == | |||
<references/> | |||
__TOC__ | __TOC__ | ||
</StructureSection> | </StructureSection> | ||
[[Category: Large Structures]] | [[Category: Large Structures]] | ||
[[Category: Streptomyces sp. BC16019]] | |||
[[Category: Koehnke J]] | [[Category: Koehnke J]] | ||
[[Category: Sikandar A]] | [[Category: Sikandar A]] | ||
Latest revision as of 15:56, 24 January 2024
Structure of the Bottromycin epimerase BotH in complex with substrateStructure of the Bottromycin epimerase BotH in complex with substrate
Structural highlights
FunctionPublication Abstract from PubMedD-amino acids endow peptides with diverse, desirable properties, but the post-translational and site-specific epimerization of L-amino acids into their D-counterparts is rare and chemically challenging. Bottromycins are ribosomally synthesized and post-translationally modified peptides that have overcome this challenge and feature a D-aspartate (D-Asp), which was proposed to arise spontaneously during biosynthesis. We have identified the highly unusual alpha/beta-hydrolase (ABH) fold enzyme BotH as a peptide epimerase responsible for the post-translational epimerization of L-Asp to D-Asp during bottromycin biosynthesis. The biochemical characterization of BotH combined with the structures of BotH and the BotH-substrate complex allowed us to propose a mechanism for this reaction. Bioinformatic analyses of BotH homologs show that similar ABH enzymes are found in diverse biosynthetic gene clusters. This places BotH as the founding member of a group of atypical ABH enzymes that may be able to epimerize non-Asp stereocenters across different families of secondary metabolites. The bottromycin epimerase BotH defines a group of atypical alpha/beta-hydrolase-fold enzymes.,Sikandar A, Franz L, Adam S, Santos-Aberturas J, Horbal L, Luzhetskyy A, Truman AW, Kalinina OV, Koehnke J Nat Chem Biol. 2020 Sep;16(9):1013-1018. doi: 10.1038/s41589-020-0569-y. Epub, 2020 Jun 29. PMID:32601484[1] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. References
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