OCA at 08:53, 21 February 2024

OCA — Wed, 21 Feb 2024 08:53:30 GMT

←Older revision		Revision as of 08:53, 21 February 2024
Line 1:		Line 1:
-	'''Unreleased structure'''

-	The ~~entry~~ 8cg4 is ~~ON HOLD until Paper Publication~~	+	==The organise full-length structure of the fungal non-reducing polyketide synthase (NR-PKS) PksA==
-		+	<StructureSection load='8cg4' size='340' side='right'caption='[[8cg4]], [[Resolution\|resolution]] 2.60Å' scene=''>
-	~~Authors~~: ~~Munoz~~-~~Hernandez~~, H., ~~Maier~~, T.	+	== Structural highlights ==
-		+	<table><tr><td colspan='2'>[[8cg4]] is a 2 chain structure with sequence from [https://en.wikipedia.org/wiki/Aspergillus_parasiticus Aspergillus parasiticus]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=8CG4 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=8CG4 FirstGlance]. <br>
-	~~Description~~: ~~The organise full~~-~~length structure~~ of the fungal ~~non~~-~~reducing polyketide~~ synthase (NR-~~PKS~~) ~~PksA~~	+	</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models\|Method:]]</b></td><td class="sblockDat" id="methodDat">Electron Microscopy, [[Resolution\|Resolution]] 2.6Å</td></tr>
-	[[Category: ~~Unreleased~~ Structures]]	+	<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=8cg4 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=8cg4 OCA], [https://pdbe.org/8cg4 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=8cg4 RCSB], [https://www.ebi.ac.uk/pdbsum/8cg4 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=8cg4 ProSAT]</span></td></tr>
-	[[Category: Maier, T]]	+	</table>
-	[[Category: Munoz-Hernandez, H]]	+	== Function ==
		+	[https://www.uniprot.org/uniprot/AFLC_ASPPU AFLC_ASPPU] Norsolorinic acid synthase; part of the gene cluster that mediates the biosynthesis of aflatoxins, a group of polyketide-derived furanocoumarins, and part of the most toxic and carcinogenic compounds among the known mycotoxins (PubMed:7592391, PubMed:15094053, PubMed:7565588, PubMed:15006741, PubMed:17086560, PubMed:18403714). The four major aflatoxins produced by A.parasiticus are aflatoxin B1 (AFB1), aflatoxin B2 (AFB2), aflatoxin G1 (AFG1) and aflatoxin G2 (AFG2) (PubMed:15006741). Within the aflatoxin pathway, the norsolorinic acid synthase aflC combines a hexanoyl starter unit provided to the acyl-carrier protein (ACP) domain by the fungal fatty acid synthase aflA/aflB, and 7 malonyl-CoA extender units to synthesize the precursor norsolorinic acid (NOR) (PubMed:17086560, PubMed:18403714). The biosynthesis of aflatoxins begins with the norsolorinic acid synthase aflC that combines a hexanoyl starter unit produced by the fatty acid synthase aflA/aflB and 7 malonyl-CoA extender units to synthesize the precursor NOR. The second step is the conversion of NOR to averantin (AVN) and requires the norsolorinic acid ketoreductase aflD, which catalyzes the dehydration of norsolorinic acid to form (1'S)-averantin. The norsolorinic acid reductases aflE and aflF may also play a role in the conversion of NOR to AVN. The cytochrome P450 monooxygenase aflG then catalyzes the hydroxylation of AVN to 5'hydroxyaverantin (HAVN). The next step is performed by the 5'-hydroxyaverantin dehydrogenase aflH that transforms HAVN to 5'-oxoaverantin (OAVN) which is further converted to averufin (AVF) by aflK that plays a dual role in the pathway, as a 5'-oxoaverantin cyclase that mediates conversion of 5'-oxoaverantin, as well as a versicolorin B synthase in a later step in the pathway. The averufin oxidase aflI catalyzes the conversion of AVF to versiconal hemiacetal acetate (VHA). VHA is then the substrate for the versiconal hemiacetal acetate esterase aflJ to yield versiconal (VAL). Versicolorin B synthase aflK then converts VAL to versicolorin B (VERB) by closing the bisfuran ring of aflatoxin which is required for DNA-binding, thus giving to aflatoxin its activity as a mutagen. Then, the activity of the versicolorin B desaturase aflL leads to versicolorin A (VERA). A branch point starts from VERB since it can also be converted to dihydrodemethylsterigmatocystin (DMDHST), probably also by aflL, VERA being a precursor for aflatoxins B1 and G1, and DMDHST for aflatoxins B2 and G2. Next, the versicolorin reductase aflM and the cytochrome P450 monooxygenase aflN are involved in conversion of VERA to demethylsterigmatocystin (DMST). AflX and aflY seem also involved in this step, through probable aflX-mediated epoxide ring-opening step following versicolorin A oxidation and aflY-mediated Baeyer-Villiger oxidation required for the formation of the xanthone ring. The methyltransferase aflO then leads to the modification of DMST to sterigmatocystin (ST), and of DMDHST to dihydrosterigmatocystin (DHST). Both ST and DHST are then substrates of the O-methyltransferase aflP to yield O-methylsterigmatocystin (OMST) and dihydro-O-methylsterigmatocystin (DHOMST), respectively. Finally OMST is converted to aflatoxins B1 and G1, and DHOMST to aflatoxins B2 and G2, via the action of several enzymes including O-methylsterigmatocystin oxidoreductase aflQ, the cytochrome P450 monooxygenase aflU, but also the NADH-dependent flavin oxidoreductase nadA which is specifically required for the synthesis of AFG1 (PubMed:15006741).<ref>PMID:17086560</ref> <ref>PMID:18403714</ref> <ref>PMID:7565588</ref> <ref>PMID:7592391</ref> <ref>PMID:15006741</ref> <ref>PMID:15094053</ref>
		+	== References ==
		+	<references/>
		+	__TOC__
		+	</StructureSection>
		+	[[Category: Aspergillus parasiticus]]
		+	[[Category: Large Structures]]
		+	[[Category: Maier T]]
		+	[[Category: Munoz-Hernandez H]]

OCA at 07:57, 21 June 2023

OCA — Wed, 21 Jun 2023 07:57:32 GMT

←Older revision		Revision as of 07:57, 21 June 2023
Line 1:		Line 1:
	'''Unreleased structure'''		'''Unreleased structure'''

-	The entry 8cg4 is ON HOLD	+	The entry 8cg4 is ON HOLD until Paper Publication

	Authors: Munoz-Hernandez, H., Maier, T.		Authors: Munoz-Hernandez, H., Maier, T.

OCA: Protected "8cg4" [edit=sysop:move=sysop]

OCA — Wed, 15 Feb 2023 08:33:39 GMT

Protected "8cg4" [edit=sysop:move=sysop]

←Older revision

Revision as of 08:33, 15 February 2023

OCA: New page: '''Unreleased structure''' The entry 8cg4 is ON HOLD Authors: Munoz-Hernandez, H., Maier, T. Description: The organise full-length structure of the fungal non-reducing polyketide synth...

OCA — Wed, 15 Feb 2023 08:33:38 GMT

New page: '''Unreleased structure''' The entry 8cg4 is ON HOLD Authors: Munoz-Hernandez, H., Maier, T. Description: The organise full-length structure of the fungal non-reducing polyketide synth...

New page

'''Unreleased structure'''

The entry 8cg4 is ON HOLD

Authors: Munoz-Hernandez, H., Maier, T.

Description: The organise full-length structure of the fungal non-reducing polyketide synthase (NR-PKS) PksA
[[Category: Unreleased Structures]]
[[Category: Maier, T]]
[[Category: Munoz-Hernandez, H]]

8cg4 - Revision history

OCA at 08:53, 21 February 2024

OCA at 07:57, 21 June 2023

OCA: Protected "8cg4" [edit=sysop:move=sysop]

OCA: New page: '''Unreleased structure''' The entry 8cg4 is ON HOLD Authors: Munoz-Hernandez, H., Maier, T. Description: The organise full-length structure of the fungal non-reducing polyketide synth...