8hk0: Difference between revisions
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New page: '''Unreleased structure''' The entry 8hk0 is ON HOLD Authors: Description: Category: Unreleased Structures |
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==Crystal structure of Fic32-33 complex from Streptomyces ficellus NRRL 8067== | |||
<StructureSection load='8hk0' size='340' side='right'caption='[[8hk0]], [[Resolution|resolution]] 2.29Å' scene=''> | |||
== Structural highlights == | |||
<table><tr><td colspan='2'>[[8hk0]] is a 4 chain structure with sequence from [https://en.wikipedia.org/wiki/Streptomyces_ficellus Streptomyces ficellus]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=8HK0 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=8HK0 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]] 2.29Å</td></tr> | |||
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=1PE:PENTAETHYLENE+GLYCOL'>1PE</scene>, <scene name='pdbligand=FAD:FLAVIN-ADENINE+DINUCLEOTIDE'>FAD</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=8hk0 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=8hk0 OCA], [https://pdbe.org/8hk0 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=8hk0 RCSB], [https://www.ebi.ac.uk/pdbsum/8hk0 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=8hk0 ProSAT]</span></td></tr> | |||
</table> | |||
== Function == | |||
[https://www.uniprot.org/uniprot/A0A1W5T2G8_9ACTN A0A1W5T2G8_9ACTN] | |||
<div style="background-color:#fffaf0;"> | |||
== Publication Abstract from PubMed == | |||
Ficellomycin, azinomycins, and vazabitide A are nonribosomal peptide natural products characterized by an amino acid unit that contains a similar 1-azabicyclo[3.1.0]hexane (ABCH) pharmacophore. This unit is derived from diamino-dihydroxy-heptanic acid (DADH); however, the process through which linear DADH is cyclized to furnish an ABCH ring system remains poorly understood. Based on the reconstitution of the route of the ABCH-containing unit by blending genes/enzymes involved in the biosynthesis of ficellomycin and azinomycins, we report that ABCH formation is completed by an oxidase heterotetramer with the association of a nonribosomal peptide synthetase (NRPS). The DADH precursor was prepared in Escherichia coli to produce a conjugate subjected to in vitro enzymatic hydrolysis for offloading from an amino-group carrier protein. To furnish an aziridine ring, DADH was processed by C7-hydroxyl sulfonation and sulfate elimination-coupled cyclization. Further cyclization leading to an azabicyclic hexane pharmacophore was proved to occur in the NRPS, where the oxidase heterotetramer functions in trans and catalyzes alpha,beta-dehydrogenation to initiate the formation of a fused five-membered nitrogen heterocycle. The identity of ABCH was validated by utilization of the resultant ABCH-containing unit in the total biosynthesis of ficellomycin. Biochemical characterization, crystal structure, and site-specific mutagenesis rationalize the catalytic mechanism of the unusual oxidase heterotetramer. | |||
Oxidase Heterotetramer Completes 1-Azabicyclo[3.1.0]hexane Formation with the Association of a Nonribosomal Peptide Synthetase.,Cheng Y, Yi X, Zhang Y, He Q, Chen D, Cao W, Fang P, Liu W J Am Chem Soc. 2023 Apr 26;145(16):8896-8907. doi: 10.1021/jacs.2c12507. Epub , 2023 Apr 12. PMID:37043819<ref>PMID:37043819</ref> | |||
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | |||
[[Category: | </div> | ||
<div class="pdbe-citations 8hk0" style="background-color:#fffaf0;"></div> | |||
== References == | |||
<references/> | |||
__TOC__ | |||
</StructureSection> | |||
[[Category: Large Structures]] | |||
[[Category: Streptomyces ficellus]] | |||
[[Category: Cheng Y]] | |||
[[Category: Fang P]] | |||
[[Category: Liu W]] | |||
[[Category: Qiao H]] | |||