View source for 8gqa


==Crystal structure of lasso peptide epimerase MslH in complexed with precursor peptide analog MslAdeltaW21==
<StructureSection load='8gqa' size='340' side='right'caption='[[8gqa]], [[Resolution|resolution]] 2.29&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[8gqa]] is a 2 chain structure with sequence from [https://en.wikipedia.org/wiki/Streptomyces_sp. Streptomyces sp.]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=8GQA OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=8GQA 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]] 2.29&#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=8gqa FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=8gqa OCA], [https://pdbe.org/8gqa PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=8gqa RCSB], [https://www.ebi.ac.uk/pdbsum/8gqa PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=8gqa ProSAT]</span></td></tr>
</table>
== Function ==
[https://www.uniprot.org/uniprot/3CP2_STRSQ 3CP2_STRSQ] Inhibits chicken myosin light chain kinase with an IC(50) of 8 M. Does not inhibit bovine cAMP-dependent protein kinase or rat protein kinase C. Antibacterial activity against the Gram-positive bacteria B.subtilis, E.faecium and S.aureus. No antibacterial activity against the Gram-negative bacteria E.coli, K.pneumoniae, P.aeruginosa, P.vulgaris, S.sonnei and S.typhosa. No antifungal activity against C.albicans.<ref>PMID:8689231</ref> 
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== 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>
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<div class="pdbe-citations 8gqa" style="background-color:#fffaf0;"></div>
== References ==
<references/>
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</StructureSection>
[[Category: Large Structures]]
[[Category: Streptomyces sp]]
[[Category: Morita H]]
[[Category: Nakashima Y]]