View source for 6azt


==Asparaginyl endopeptidase 1 bound to AAN peptide, a tetrahedral intermediate==
<StructureSection load='6azt' size='340' side='right'caption='[[6azt]], [[Resolution|resolution]] 1.80&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[6azt]] is a 2 chain structure with sequence from [https://en.wikipedia.org/wiki/Helianthus_annuus Helianthus annuus] and [https://en.wikipedia.org/wiki/Synthetic_construct Synthetic construct]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6AZT OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=6AZT 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]] 1.8&#8491;</td></tr>
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=CE7:(3S)-3-amino-4,4,4-trihydroxybutanamide'>CE7</scene>, <scene name='pdbligand=GOL:GLYCEROL'>GOL</scene>, <scene name='pdbligand=SNN:L-3-AMINOSUCCINIMIDE'>SNN</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=6azt FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6azt OCA], [https://pdbe.org/6azt PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=6azt RCSB], [https://www.ebi.ac.uk/pdbsum/6azt PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=6azt ProSAT]</span></td></tr>
</table>
== Function ==
[https://www.uniprot.org/uniprot/A0A251RPF5_HELAN A0A251RPF5_HELAN] 
<div style="background-color:#fffaf0;">
== Publication Abstract from PubMed ==
Constrained, cyclic peptides encoded by plant genes represent a new generation of drug leads. Evolution has repeatedly recruited the Cys-protease asparaginyl endopeptidase (AEP) to perform their head-to-tail ligation. These macrocyclization reactions use the substrates amino terminus instead of water to deacylate, so a peptide bond is formed. How solvent-exposed plant AEPs macrocyclize is poorly understood. Here we present the crystal structure of an active plant AEP from the common sunflower, Helianthus annuus. The active site contained electron density for a tetrahedral intermediate with partial occupancy that predicted a binding mode for peptide macrocyclization. By substituting catalytic residues we could alter the ratio of cyclic to acyclic products. Moreover, we showed AEPs from other species lacking cyclic peptides can perform macrocyclization under favorable pH conditions. This structural characterization of AEP presents a logical framework for engineering superior enzymes that generate macrocyclic peptide drug leads.

Structural basis of ribosomal peptide macrocyclization in plants.,Haywood J, Schmidberger JW, James AM, Nonis SG, Sukhoverkov KV, Elias M, Bond CS, Mylne JS Elife. 2018 Jan 31;7. pii: 32955. doi: 10.7554/eLife.32955. PMID:29384475<ref>PMID:29384475</ref>

From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
</div>
<div class="pdbe-citations 6azt" style="background-color:#fffaf0;"></div>
== References ==
<references/>
__TOC__
</StructureSection>
[[Category: Helianthus annuus]]
[[Category: Large Structures]]
[[Category: Synthetic construct]]
[[Category: Bond CS]]