View source for 8itg


==Crystal structure of lasso peptide epimerase MslH in complexed with precursor peptide variant MslAW21G==
<StructureSection load='8itg' size='340' side='right'caption='[[8itg]], [[Resolution|resolution]] 2.25&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[8itg]] is a 2 chain structure with sequence from [https://en.wikipedia.org/wiki/Streptomyces_griseorubiginosus Streptomyces griseorubiginosus]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=8ITG OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=8ITG 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]] 2.25&#8491;</td></tr>
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=CA:CALCIUM+ION'>CA</scene>, <scene name='pdbligand=TRS:2-AMINO-2-HYDROXYMETHYL-PROPANE-1,3-DIOL'>TRS</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=8itg FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=8itg OCA], [https://pdbe.org/8itg PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=8itg RCSB], [https://www.ebi.ac.uk/pdbsum/8itg PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=8itg ProSAT]</span></td></tr>
</table>
<div style="background-color:#fffaf0;">
== Publication Abstract from PubMed ==
The lasso peptide MS-271 is a ribosomally synthesized and post-translationally modified peptide (RiPP) consisting of 21 amino acids with D-tryptophan at the C-terminus, and is derived from the precursor peptide MslA. MslH, encoded in the MS-271 biosynthetic gene cluster (msl), catalyzes the epimerization at the Calpha center of the MslA C-terminal Trp21, leading to epi-MslA. The detailed catalytic process, including the catalytic site and cofactors, has remained enigmatic. Herein, based on X-ray crystallographic studies in association with MslA core peptide analogues, we show that MslH is a metallo-dependent peptide epimerase with a calcineurin-like fold. The crystal structure analysis, followed by site-directed mutagenesis, docking simulation, and ICP-MS studies demonstrate that MslH employs acid/base chemistry to facilitate the reversible epimerization of the C-terminal Trp21 of MslA, by utilizing two pairs of His/Asp catalytic residues that are electrostatically tethered to a six-coordination motif with a Ca(II) ion via water molecules.

Structure of lasso peptide epimerase MslH reveals metal-dependent acid/base catalytic mechanism.,Nakashima Y, Kawakami A, Ogasawara Y, Maeki M, Tokeshi M, Dairi T, Morita H Nat Commun. 2023 Aug 8;14(1):4752. doi: 10.1038/s41467-023-40232-x. PMID:37550286<ref>PMID:37550286</ref>

From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
</div>
<div class="pdbe-citations 8itg" style="background-color:#fffaf0;"></div>
== References ==
<references/>
__TOC__
</StructureSection>
[[Category: Large Structures]]
[[Category: Streptomyces griseorubiginosus]]
[[Category: Hiroyuki M]]
[[Category: Nakashima Y]]