9w0a: Difference between revisions

Line 1:

~~'''Unreleased structure'''~~

~~The entry~~ 9w0a is ~~ON HOLD until Paper~~ Publication

==Wild-type P450 enzyme-TtpB1==

== Structural highlights ==

<table><tr><td colspan='2'>[[9w0a]] is a 1 chain structure with sequence from [https://en.wikipedia.org/wiki/Escherichia_coli Escherichia coli]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=9W0A OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=9W0A 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]] 2.48Å</td></tr>

<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=A1EUF:(3~{S},6~{S})-3,6-bis[(6-chloranyl-1~{H}-indol-3-yl)methyl]piperazine-2,5-dione'>A1EUF</scene>, <scene name='pdbligand=HEM:PROTOPORPHYRIN+IX+CONTAINING+FE'>HEM</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=9w0a FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=9w0a OCA], [https://pdbe.org/9w0a PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=9w0a RCSB], [https://www.ebi.ac.uk/pdbsum/9w0a PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=9w0a ProSAT]</span></td></tr>

</table>

== Publication Abstract from PubMed ==

Bispyrrolidinoindoline-diketopiperazines (BPI-DKP) alkaloids, characterized by a complex 3a,3a'-bispyrrolidino[2,3-b]indoline scaffold, constitute a large class of synthetically challenging bioactive pyrroloindoline natural products. Their biosynthesis, mediated by P450 enzymes, involves oxidative dimerization of diketopiperazines (DKPs), yet the underlying mechanistic and stereochemical details have remained unclear. Here, we elucidate the molecular mechanism of TtpB1, a P450 dimerase that stereoselectively couples two DKP units to form C(2)-symmetric BPI scaffolds through an unexpected cascade. Contrary to the prevailing double-radical coupling hypothesis, integrated structural, biochemical, and computational studies reveal a stepwise process: (i) Compound I-mediated generation of a nitrogen-centered DKP radical, triggering cyclization to a C3-radical pyrroloindoline intermediate; (ii) radical addition to the C3' position of a second DKP; and (iii) single-electron transfer (SET)-driven cyclization to construct the second pyrroloindoline unit. This dual N-centered radical- and SET-driven cyclization showcases unprecedented versatility in natural product dimer biosynthesis. Molecular dynamics and QM/MM calculations further demonstrate how substrate conformational dynamics enforce stereochemical fidelity, yielding the C(2)-symmetric BPI-DKP core with vicinal quaternary stereocenters. These findings provide the first structure-guided mechanistic elucidation of BPI-DKP synthase, laying the groundwork for rational enzyme engineering and biomimetic synthesis of these pharmacologically important alkaloids.

~~Authors~~:

P450-Mediated Dual Cyclization Mechanisms for Pyrroloindoline Unit Formation in Bispyrrolidinoindoline Diketopiperazine Alkaloid Biosynthesis.,Du Y, Wei G, Zhou TP, Dai Y, Tian W, Tang M, Deng Z, Wang B, Qu X J Am Chem Soc. 2025 Dec 10;147(49):45199-45209. doi: 10.1021/jacs.5c14741. Epub , 2025 Dec 1. PMID:41326270<ref>PMID:41326270</ref>

~~Description~~:

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br>

[[Category: ~~Unreleased~~ Structures]]

</div>

== References ==

__TOC__

</StructureSection>

[[Category: Escherichia coli]]

[[Category: Large Structures]]

[[Category: Du YQ]]

[[Category: Qu XD]]

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@@ Line 1: / Line 1: @@
-'''Unreleased structure'''
-The entry 9w0a is ON HOLD  until Paper Publication
+==Wild-type P450 enzyme-TtpB1==
+<StructureSection load='9w0a' size='340' side='right'caption='[[9w0a]], [[Resolution|resolution]] 2.48&Aring;' scene=''>
+== Structural highlights ==
+<table><tr><td colspan='2'>[[9w0a]] is a 1 chain structure with sequence from [https://en.wikipedia.org/wiki/Escherichia_coli Escherichia coli]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=9W0A OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=9W0A 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]] 2.48&#8491;</td></tr>
+<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=A1EUF:(3~{S},6~{S})-3,6-bis[(6-chloranyl-1~{H}-indol-3-yl)methyl]piperazine-2,5-dione'>A1EUF</scene>, <scene name='pdbligand=HEM:PROTOPORPHYRIN+IX+CONTAINING+FE'>HEM</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=9w0a FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=9w0a OCA], [https://pdbe.org/9w0a PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=9w0a RCSB], [https://www.ebi.ac.uk/pdbsum/9w0a PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=9w0a ProSAT]</span></td></tr>
+</table>
+<div style="background-color:#fffaf0;">
+== Publication Abstract from PubMed ==
+Bispyrrolidinoindoline-diketopiperazines (BPI-DKP) alkaloids, characterized by a complex 3a,3a'-bispyrrolidino[2,3-b]indoline scaffold, constitute a large class of synthetically challenging bioactive pyrroloindoline natural products. Their biosynthesis, mediated by P450 enzymes, involves oxidative dimerization of diketopiperazines (DKPs), yet the underlying mechanistic and stereochemical details have remained unclear. Here, we elucidate the molecular mechanism of TtpB1, a P450 dimerase that stereoselectively couples two DKP units to form C(2)-symmetric BPI scaffolds through an unexpected cascade. Contrary to the prevailing double-radical coupling hypothesis, integrated structural, biochemical, and computational studies reveal a stepwise process: (i) Compound I-mediated generation of a nitrogen-centered DKP radical, triggering cyclization to a C3-radical pyrroloindoline intermediate; (ii) radical addition to the C3' position of a second DKP; and (iii) single-electron transfer (SET)-driven cyclization to construct the second pyrroloindoline unit. This dual N-centered radical- and SET-driven cyclization showcases unprecedented versatility in natural product dimer biosynthesis. Molecular dynamics and QM/MM calculations further demonstrate how substrate conformational dynamics enforce stereochemical fidelity, yielding the C(2)-symmetric BPI-DKP core with vicinal quaternary stereocenters. These findings provide the first structure-guided mechanistic elucidation of BPI-DKP synthase, laying the groundwork for rational enzyme engineering and biomimetic synthesis of these pharmacologically important alkaloids.
-Authors:
+P450-Mediated Dual Cyclization Mechanisms for Pyrroloindoline Unit Formation in Bispyrrolidinoindoline Diketopiperazine Alkaloid Biosynthesis.,Du Y, Wei G, Zhou TP, Dai Y, Tian W, Tang M, Deng Z, Wang B, Qu X J Am Chem Soc. 2025 Dec 10;147(49):45199-45209. doi: 10.1021/jacs.5c14741. Epub , 2025 Dec 1. PMID:41326270<ref>PMID:41326270</ref>
-Description:
+From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
-[[Category: Unreleased Structures]]
+</div>
+<div class="pdbe-citations 9w0a" style="background-color:#fffaf0;"></div>
+== References ==
+<references/>
+__TOC__
+</StructureSection>
+[[Category: Escherichia coli]]
+[[Category: Large Structures]]
+[[Category: Du YQ]]
+[[Category: Qu XD]]