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3wxy

From Proteopedia

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Current revision

Crystal structure of CsyB complexed with CoA-SH

Structural highlights

3wxy is a 2 chain structure with sequence from Aspergillus oryzae. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Method:	X-ray diffraction, Resolution 1.706Å
Ligands:
Resources:	FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Function

CSYB_ASPOR Acylalkylpyrone synthase that catalyzes not only the polyketide chain elongation but also the one-pot condensation of two beta-ketoacyl units to produce the 3-acyl-4-hydroxy-6-alkyl-alpha-pyrone (AcAP) scaffold, a precursor of csypyrone B (PubMed:20471846, PubMed:23290452, PubMed:24011646, PubMed:24895122, PubMed:25564614) (Probable). The enzyme reaction is initiated by the loading of acetoacetyl-CoA onto Cys-155, and subsequent thioester bond cleavage by the nucleophilic water generates the beta-keto acid intermediate, which is placed within a pocket (PubMed:25564614). The second beta-ketoacyl unit is then produced by polyketide chain elongation of fatty acyl-CoA with one molecule of malonyl-CoA, and the condensation with the beta-ketoacid generates the final products (PubMed:24895122, PubMed:25564614). Csypyrone B1 is the major product and contains a propanoic acid side-chain, whereas csypyrones B2 and B3 are minor compounds that contain butyric or pentanoic acid side-chains, respectively (PubMed:20471846, PubMed:23290452, PubMed:24011646).^[1] ^[2] ^[3] ^[4] ^[5] ^[6]

Publication Abstract from PubMed

The acylalkylpyrone synthase CsyB from Aspergillus oryzae catalyzes the one-pot formation of the 3-acyl-4-hydroxy-6-alkyl-alpha-pyrone scaffold from acetoacetyl-CoA, fatty acyl-CoA, and malonyl-CoA. This is the first type III polyketide synthase that performs not only the polyketide chain elongation but also the condensation of two beta-ketoacyl units. The crystal structures of wild-type CsyB and its I375F and I375W mutants were solved at 1.7-, 2.3-, and 2.0-A resolutions, respectively. The crystal structures revealed a unique active site architecture featuring a hitherto unidentified novel pocket for accommodation of the acetoacetyl-CoA starter in addition to the conventional elongation/cyclization pocket with the Cys-His-Asn catalytic triad and the long hydrophobic tunnel for binding the fatty acyl chain. The structures also indicated the presence of a putative nucleophilic water molecule activated by the hydrogen bond networks with His-377 and Cys-155 at the active site center. Furthermore, an in vitro enzyme reaction confirmed that the (18)O atom of the H2(18)O molecule is enzymatically incorporated into the final product. These observations suggested that the enzyme reaction is initiated by the loading of acetoacetyl-CoA onto Cys-155, and subsequent thioester bond cleavage by the nucleophilic water generates the beta-keto acid intermediate, which is placed within the novel pocket. The second beta-ketoacyl unit is then produced by polyketide chain elongation of fatty acyl-CoA with one molecule of malonyl-CoA, and the condensation with the beta-keto acid generates the final products. Indeed, steric modulation of the novel pocket by the structure-based I375F and I375W mutations resulted in altered specificities for the chain lengths of the substrates.

Structural basis for the formation of acylalkylpyrones from two beta-ketoacyl units by the fungal type III polyketide synthase CsyB.,Mori T, Yang D, Matsui T, Hashimoto M, Morita H, Fujii I, Abe I J Biol Chem. 2015 Feb 20;290(8):5214-25. doi: 10.1074/jbc.M114.626416. Epub 2015 , Jan 6. PMID:25564614^[7]

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

References

↑ Seshime Y, Juvvadi PR, Kitamoto K, Ebizuka Y, Fujii I. Identification of csypyrone B1 as the novel product of Aspergillus oryzae type III polyketide synthase CsyB. Bioorg Med Chem. 2010 Jun 15;18(12):4542-6. PMID:20471846 doi:10.1016/j.bmc.2010.04.058
↑ Hashimoto M, Seshime Y, Kitamoto K, Uchiyama N, Goda Y, Fujii I. Identification of csypyrone B2 and B3 as the minor products of Aspergillus oryzae type III polyketide synthase CsyB. Bioorg Med Chem Lett. 2013 Feb 1;23(3):650-3. PMID:23290452 doi:10.1016/j.bmcl.2012.11.119
↑ Hashimoto M, Ishida S, Seshime Y, Kitamoto K, Fujii I. Aspergillus oryzae type III polyketide synthase CsyB uses a fatty acyl starter for the biosynthesis of csypyrone B compounds. Bioorg Med Chem Lett. 2013 Oct 15;23(20):5637-40. PMID:24011646 doi:10.1016/j.bmcl.2013.08.036
↑ Hashimoto M, Koen T, Takahashi H, Suda C, Kitamoto K, Fujii I. Aspergillus oryzae CsyB catalyzes the condensation of two β-ketoacyl-CoAs to form 3-acetyl-4-hydroxy-6-alkyl-α-pyrone. J Biol Chem. 2014 Jul 18;289(29):19976-84. PMID:24895122 doi:10.1074/jbc.M114.569095
↑ Mori T, Yang D, Matsui T, Hashimoto M, Morita H, Fujii I, Abe I. Structural basis for the formation of acylalkylpyrones from two beta-ketoacyl units by the fungal type III polyketide synthase CsyB. J Biol Chem. 2015 Feb 20;290(8):5214-25. doi: 10.1074/jbc.M114.626416. Epub 2015 , Jan 6. PMID:25564614 doi:http://dx.doi.org/10.1074/jbc.M114.626416
↑ Yang D, Mori T, Matsui T, Hashimoto M, Morita H, Fujii I, Abe I. Expression, purification and crystallization of a fungal type III polyketide synthase that produces the csypyrones. Acta Crystallogr F Struct Biol Commun. 2014 Jun;70(Pt 6):730-3. PMID:24915080 doi:10.1107/S2053230X14008516
↑ Mori T, Yang D, Matsui T, Hashimoto M, Morita H, Fujii I, Abe I. Structural basis for the formation of acylalkylpyrones from two beta-ketoacyl units by the fungal type III polyketide synthase CsyB. J Biol Chem. 2015 Feb 20;290(8):5214-25. doi: 10.1074/jbc.M114.626416. Epub 2015 , Jan 6. PMID:25564614 doi:http://dx.doi.org/10.1074/jbc.M114.626416

1 Structural highlights
2 Function
3 Publication Abstract from PubMed
4 References

Proteopedia Page Contributors and Editors (what is this?)

OCA

Retrieved from "http://52.214.119.220/wiki/index.php/3wxy"

@@ Line 3: / Line 3: @@
 <StructureSection load='3wxy' size='340' side='right'caption='[[3wxy]], [[Resolution|resolution]] 1.71&Aring;' scene=''>
 == Structural highlights ==
-<table><tr><td colspan='2'>[[3wxy]] is a 2 chain structure with sequence from [http://en.wikipedia.org/wiki/Aspoz Aspoz]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3WXY OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=3WXY FirstGlance]. <br>
+<table><tr><td colspan='2'>[[3wxy]] is a 2 chain structure with sequence from [https://en.wikipedia.org/wiki/Aspergillus_oryzae Aspergillus oryzae]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3WXY OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=3WXY FirstGlance]. <br>
-</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=COA:COENZYME+A'>COA</scene></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]] 1.706&#8491;</td></tr>
-<tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[3wxz|3wxz]], [[3wy0|3wy0]]</td></tr>
+<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=COA:COENZYME+A'>COA</scene></td></tr>
-<tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">csyB ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=5062 ASPOZ])</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=3wxy FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3wxy OCA], [https://pdbe.org/3wxy PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=3wxy RCSB], [https://www.ebi.ac.uk/pdbsum/3wxy PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=3wxy ProSAT]</span></td></tr>
-<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=3wxy FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3wxy OCA], [http://pdbe.org/3wxy PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=3wxy RCSB], [http://www.ebi.ac.uk/pdbsum/3wxy PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=3wxy ProSAT]</span></td></tr>
 </table>
+== Function ==
+[https://www.uniprot.org/uniprot/CSYB_ASPOR CSYB_ASPOR] Acylalkylpyrone synthase that catalyzes not only the polyketide chain elongation but also the one-pot condensation of two beta-ketoacyl units to produce the 3-acyl-4-hydroxy-6-alkyl-alpha-pyrone (AcAP) scaffold, a precursor of csypyrone B (PubMed:20471846, PubMed:23290452, PubMed:24011646, PubMed:24895122, PubMed:25564614) (Probable). The enzyme reaction is initiated by the loading of acetoacetyl-CoA onto Cys-155, and subsequent thioester bond cleavage by the nucleophilic water generates the beta-keto acid intermediate, which is placed within a pocket (PubMed:25564614). The second beta-ketoacyl unit is then produced by polyketide chain elongation of fatty acyl-CoA with one molecule of malonyl-CoA, and the condensation with the beta-ketoacid generates the final products (PubMed:24895122, PubMed:25564614). Csypyrone B1 is the major product and contains a propanoic acid side-chain, whereas csypyrones B2 and B3 are minor compounds that contain butyric or pentanoic acid side-chains, respectively (PubMed:20471846, PubMed:23290452, PubMed:24011646).<ref>PMID:20471846</ref> <ref>PMID:23290452</ref> <ref>PMID:24011646</ref> <ref>PMID:24895122</ref> <ref>PMID:25564614</ref> <ref>PMID:24915080</ref>
 <div style="background-color:#fffaf0;">
 == Publication Abstract from PubMed ==
@@ Line 22: / Line 23: @@
 __TOC__
 </StructureSection>
-[[Category: Aspoz]]
+[[Category: Aspergillus oryzae]]
 [[Category: Large Structures]]
-[[Category: Abe, I]]
+[[Category: Abe I]]
-[[Category: Fujii, I]]
+[[Category: Fujii I]]
-[[Category: Matsui, T]]
+[[Category: Matsui T]]
-[[Category: Mori, T]]
+[[Category: Mori T]]
-[[Category: Morita, H]]
+[[Category: Morita H]]
-[[Category: Yang, D]]
+[[Category: Yang D]]
-[[Category: Acyltransferase]]
-[[Category: Csyb]]
-[[Category: Transferase]]
-[[Category: Type iii polyketide synthase]]

3wxy

From Proteopedia

Current revision

Crystal structure of CsyB complexed with CoA-SH

Structural highlights

Function

Publication Abstract from PubMed

References

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Proteopedia Page Contributors and Editors (what is this?)

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