View source for 6mw0


==Mle-Phe-Mle-D-Phe. Linear tetrapeptide related to pseudoxylallemycin A.==
<StructureSection load='6mw0' size='340' side='right'caption='[[6mw0]], [[Resolution|resolution]] 0.78&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[6mw0]] is a 1 chain structure with sequence from [https://en.wikipedia.org/wiki/Xylaria Xylaria]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6MW0 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=6MW0 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]] 0.78&#8491;</td></tr>
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=DPN:D-PHENYLALANINE'>DPN</scene>, <scene name='pdbligand=MLE:N-METHYLLEUCINE'>MLE</scene>, <scene name='pdbligand=MOH:METHANOL'>MOH</scene>, <scene name='pdbligand=PRD_002334:Linear+tetrapeptide+related+to+pseudoxylallemycin+A'>PRD_002334</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=6mw0 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6mw0 OCA], [https://pdbe.org/6mw0 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=6mw0 RCSB], [https://www.ebi.ac.uk/pdbsum/6mw0 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=6mw0 ProSAT]</span></td></tr>
</table>
<div style="background-color:#fffaf0;">
== Publication Abstract from PubMed ==
The total synthesis and structural confirmation of naturally occurring all l-cyclic tetrapeptide pseudoxylallemycin A is reported. X-ray crystallography revealed that the linear precursor adopted an all-trans (ttt) extended linear conformation, while its cyclic derivative adopts a trans,cis,trans,cis (tctc) conformation. Two kinetically favoured cyclic conformers prone to hydrolysis initially formed rapidly during cyclisation, with subsequent conversion to the thermodynamically stable tctc macrocycle taking place slowly. We postulate the initial unstable cyclic product undergoes an unprecedented nucleophilic ring opening with either the T3P or PyAOP by-products to give the linear ttt structure as a reactivated species and through a series of equilibria is slowly consumed by cyclisation to the thermodynamic product pseudoxylallemycin A. Consumption of the reactivated species by formation of pseudoxylallemycin A requires a trans-cis isomerism to occur and necessitates moderately increased reaction temperatures. Cyclisation with T3P was found to provide the greatest stereoretention. Synthesis and X-ray crystallography of the C-terminal epimer demonstrated its cyclisation to be kinetically favoured and to proceed without epimerisation despite also bearing an all-trans backbone.

Investigations of the key macrolactamisation step in the synthesis of cyclic tetrapeptide pseudoxylallemycin A.,Cameron AJ, Squire CJ, Gerenton A, Stubbing LA, Harris PWR, Brimble MA Org Biomol Chem. 2019 Apr 17;17(16):3902-3913. doi: 10.1039/c9ob00227h. PMID:30941386<ref>PMID:30941386</ref>

From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
</div>
<div class="pdbe-citations 6mw0" style="background-color:#fffaf0;"></div>
== References ==
<references/>
__TOC__
</StructureSection>
[[Category: Large Structures]]
[[Category: Xylaria]]
[[Category: Brimble MA]]
[[Category: Cameron AJ]]
[[Category: Harris PWR]]
[[Category: Squire CJ]]