6vy9 - Revision history

OCA at 09:16, 25 October 2023

OCA — Wed, 25 Oct 2023 09:16:25 GMT

←Older revision		Revision as of 09:16, 25 October 2023
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	== Structural highlights ==		== Structural highlights ==
	<table><tr><td colspan='2'>[[6vy9]] is a 8 chain structure with sequence from [https://en.wikipedia.org/wiki/Aspergillus_sp._MF297-2 Aspergillus sp. MF297-2]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6VY9 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=6VY9 FirstGlance]. <br>		<table><tr><td colspan='2'>[[6vy9]] is a 8 chain structure with sequence from [https://en.wikipedia.org/wiki/Aspergillus_sp._MF297-2 Aspergillus sp. MF297-2]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6VY9 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=6VY9 FirstGlance]. <br>
-	</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=6vy9 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6vy9 OCA], [https://pdbe.org/6vy9 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=6vy9 RCSB], [https://www.ebi.ac.uk/pdbsum/6vy9 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=6vy9 ProSAT]</span></td></tr>	+	</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models\|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution\|Resolution]] 3.19Å</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=6vy9 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6vy9 OCA], [https://pdbe.org/6vy9 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=6vy9 RCSB], [https://www.ebi.ac.uk/pdbsum/6vy9 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=6vy9 ProSAT]</span></td></tr>
	</table>		</table>
	== Function ==		== Function ==

OCA at 06:09, 2 March 2023

OCA — Thu, 02 Mar 2023 06:09:15 GMT

←Older revision		Revision as of 06:09, 2 March 2023
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	==Crystal structure of NotF prenyltransferase==		==Crystal structure of NotF prenyltransferase==
-	<StructureSection load='6vy9' size='340' side='right'caption='[[6vy9]]' scene=''>	+	<StructureSection load='6vy9' size='340' side='right'caption='[[6vy9]], [[Resolution\|resolution]] 3.19Å' scene=''>
	== Structural highlights ==		== Structural highlights ==
-	<table><tr><td colspan='2'>Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6VY9 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=6VY9 FirstGlance]. <br>	+	<table><tr><td colspan='2'>[[6vy9]] is a 8 chain structure with sequence from [https://en.wikipedia.org/wiki/Aspergillus_sp._MF297-2 Aspergillus sp. MF297-2]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6VY9 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=6VY9 FirstGlance]. <br>
	</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=6vy9 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6vy9 OCA], [https://pdbe.org/6vy9 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=6vy9 RCSB], [https://www.ebi.ac.uk/pdbsum/6vy9 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=6vy9 ProSAT]</span></td></tr>		</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=6vy9 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6vy9 OCA], [https://pdbe.org/6vy9 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=6vy9 RCSB], [https://www.ebi.ac.uk/pdbsum/6vy9 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=6vy9 ProSAT]</span></td></tr>
	</table>		</table>
		+	== Function ==
		+	[https://www.uniprot.org/uniprot/NOTF_ASPSM NOTF_ASPSM] Deoxybrevianamide E synthase; part of the gene cluster that mediates the biosynthesis of notoamide, a fungal indole alkaloid that belongs to a family of natural products containing a characteristic bicyclo[2.2.2]diazaoctane core (PubMed:20722388). The first step of notoamide biosynthesis involves coupling of L-proline and L-tryptophan by the bimodular NRPS notE, to produce cyclo-L-tryptophan-L-proline called brevianamide F (PubMed:20722388). The reverse prenyltransferase notF then acts as a deoxybrevianamide E synthase and converts brevianamide F to deoxybrevianamide E via reverse prenylation at C-2 of the indole ring leading to the bicyclo[2.2.2]diazaoctane core (PubMed:20722388). Deoxybrevianamide E is further hydroxylated at C-6 of the indole ring, likely catalyzed by the cytochrome P450 monooxygenase notG, to yield 6-hydroxy-deoxybrevianamide E (Probable). 6-hydroxy-deoxybrevianamide E is a specific substrate of the prenyltransferase notC for normal prenylation at C-7 to produce 6-hydroxy-7-prenyl-deoxybrevianamide, also called notoamide S (PubMed:20722388). As the proposed pivotal branching point in notoamide biosynthesis, notoamide S can be diverted to notoamide E through an oxidative pyran ring closure putatively catalyzed by either notH cytochrome P450 monooxygenase or the notD FAD-linked oxidoreductase (Probable). This step would be followed by an indole 2,3-epoxidation-initiated pinacol-like rearrangement catalyzed by the notB FAD-dependent monooxygenase leading to the formation of notoamide C and notoamide D (PubMed:22188465). On the other hand notoamide S is converted to notoamide T by notH (or notD), a bifunctional oxidase that also functions as the intramolecular Diels-Alderase responsible for generation of (+)-notoamide T (Probable). To generate antipodal (-)-notoaminide T, notH' (or notD') in Aspergillus versicolor is expected to catalyze a Diels-Alder reaction leading to the opposite stereochemistry (Probable). The remaining oxidoreductase notD (or notH) likely catalyzes the oxidative pyran ring formation to yield (+)-stephacidin A (Probable). The FAD-dependent monooxygenase notI is highly similar to notB and is predicted to catalyze a similar conversion from (+)-stephacidin A to (-)-notoamide B via the 2,3-epoxidation of (+)-stephacidin A followed by a pinacol-type rearrangement (Probable). Finally, it remains unclear which enzyme could be responsible for the final hydroxylation steps leading to notoamide A and sclerotiamide (Probable).<ref>PMID:20722388</ref> <ref>PMID:22188465</ref> <ref>PMID:23213353</ref>
		+	<div style="background-color:#fffaf0;">
		+	== Publication Abstract from PubMed ==
		+	Prenyltransfer is an early-stage carbon-hydrogen bond (C-H) functionalization prevalent in the biosynthesis of a diverse array of biologically active bacterial, fungal, plant, and metazoan diketopiperazine (DKP) alkaloids. Toward the development of a unified strategy for biocatalytic construction of prenylated DKP indole alkaloids, we sought to identify and characterize a substrate-permissive C2 reverse prenyltransferase (PT). As the first tailoring event within the biosynthesis of cytotoxic notoamide metabolites, PT NotF catalyzes C2 reverse prenyltransfer of brevianamide F. Solving a crystal structure of NotF (in complex with native substrate and prenyl donor mimic dimethylallyl S-thiolodiphosphate (DMSPP)) revealed a large, solvent-exposed active site, intimating NotF may possess a significantly broad substrate scope. To assess the substrate selectivity of NotF, we synthesized a panel of 30 sterically and electronically differentiated tryptophanyl DKPs, the majority of which were selectively prenylated by NotF in synthetically useful conversions (2 to >99%). Quantitative representation of this substrate library and development of a descriptive statistical model provided insight into the molecular origins of NotF's substrate promiscuity. This approach enabled the identification of key substrate descriptors (electrophilicity, size, and flexibility) that govern the rate of NotF-catalyzed prenyltransfer, and the development of an "induced fit docking (IFD)-guided" engineering strategy for improved turnover of our largest substrates. We further demonstrated the utility of NotF in tandem with oxidative cyclization using flavin monooxygenase, BvnB. This one-pot, in vitro biocatalytic cascade enabled the first chemoenzymatic synthesis of the marine fungal natural product, (-)-eurotiumin A, in three steps and 60% overall yield.
		+
		+	Data Science-Driven Analysis of Substrate-Permissive Diketopiperazine Reverse Prenyltransferase NotF: Applications in Protein Engineering and Cascade Biocatalytic Synthesis of (-)-Eurotiumin A.,Kelly SP, Shende VV, Flynn AR, Dan Q, Ye Y, Smith JL, Tsukamoto S, Sigman MS, Sherman DH J Am Chem Soc. 2022 Oct 26;144(42):19326-19336. doi: 10.1021/jacs.2c06631. Epub , 2022 Oct 12. PMID:36223664<ref>PMID:36223664</ref>
		+
		+	From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br>
		+	</div>
		+	<div class="pdbe-citations 6vy9" style="background-color:#fffaf0;"></div>
		+	== References ==
		+	<references/>
	__TOC__		__TOC__
	</StructureSection>		</StructureSection>
		+	[[Category: Aspergillus sp. MF297-2]]
	[[Category: Large Structures]]		[[Category: Large Structures]]
	[[Category: Dan Q]]		[[Category: Dan Q]]
	[[Category: Smith JL]]		[[Category: Smith JL]]

OCA at 11:07, 3 February 2021

OCA — Wed, 03 Feb 2021 11:07:13 GMT

←Older revision		Revision as of 11:07, 3 February 2021
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-	'''Unreleased structure'''

-	~~The entry~~ 6vy9 ~~is ON HOLD until Feb 25 2022~~	+	==Crystal structure of NotF prenyltransferase==
-		+	<StructureSection load='6vy9' size='340' side='right'caption='[[6vy9]]' scene=''>
-	~~Authors~~: ~~Dan~~, Q., ~~Smith~~, J.L.	+	== Structural highlights ==
-		+	<table><tr><td colspan='2'>Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6VY9 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=6VY9 FirstGlance]. <br>
-	~~Description: Crystal structure of NotF prenyltransferase~~	+	</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=6vy9 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6vy9 OCA], [https://pdbe.org/6vy9 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=6vy9 RCSB], [https://www.ebi.ac.uk/pdbsum/6vy9 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=6vy9 ProSAT]</span></td></tr>
-	[[Category: ~~Unreleased~~ Structures]]	+	</table>
-	[[Category: Dan, Q]]	+	__TOC__
-	[[Category: Smith~~, J.L~~]]	+	</StructureSection>
		+	[[Category: Large Structures]]
		+	[[Category: Dan Q]]
		+	[[Category: Smith JL]]

OCA at 03:55, 13 May 2020

OCA — Wed, 13 May 2020 03:55:35 GMT

←Older revision		Revision as of 03:55, 13 May 2020
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	'''Unreleased structure'''		'''Unreleased structure'''

-	The entry 6vy9 is ON HOLD	+	The entry 6vy9 is ON HOLD until Feb 25 2022

	Authors: Dan, Q., Smith, J.L.		Authors: Dan, Q., Smith, J.L.

OCA: Protected "6vy9" [edit=sysop:move=sysop]

OCA — Wed, 04 Mar 2020 05:39:46 GMT

Protected "6vy9" [edit=sysop:move=sysop]

←Older revision

Revision as of 05:39, 4 March 2020

OCA: New page: '''Unreleased structure''' The entry 6vy9 is ON HOLD Authors: Dan, Q., Smith, J.L. Description: Crystal structure of NotF prenyltransferase Category: Unreleased Structures [[Catego...

OCA — Wed, 04 Mar 2020 05:39:45 GMT

New page: '''Unreleased structure''' The entry 6vy9 is ON HOLD Authors: Dan, Q., Smith, J.L. Description: Crystal structure of NotF prenyltransferase Category: Unreleased Structures [[Catego...

New page

'''Unreleased structure'''

The entry 6vy9 is ON HOLD

Authors: Dan, Q., Smith, J.L.

Description: Crystal structure of NotF prenyltransferase
[[Category: Unreleased Structures]]
[[Category: Dan, Q]]
[[Category: Smith, J.L]]