4rzm

From Proteopedia

(Difference between revisions)

Revision as of 16:46, 21 January 2015

Crystal structure of the Lsd19-lasalocid A complex

Structural highlights

4rzm is a 2 chain structure. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Ligands:	, , , ,
Related:	3rga
Resources:	FirstGlance, OCA, RCSB, PDBsum

Function

[LSD19_STRLS] Epoxide hydrolase responsible for the double epoxide-opening cyclization of bisepoxyprelasalocid A to form lasalocid A, a polyether antibiotic. In vitro, accepts various substrate analogs differing in the left segment of lasalocid and epoxide stereochemistry to afford products with excellent regioselectivity.^[1] ^[2] ^[3] ^[4]

Publication Abstract from PubMed

Biosynthesis of some polyether natural products involves a kinetically disfavored epoxide-opening cyclic ether formation, a reaction termed anti-Baldwin cyclization. One such example is the biosynthesis of lasalocid A, an ionophore antibiotic polyether. During lasalocid A biosynthesis, an epoxide hydrolase, Lsd19, converts the bisepoxy polyketide intermediate into the tetrahydrofuranyl-tetrahydropyran product. We report the crystal structure of Lsd19 in complex with lasalocid A. The structure unambiguously shows that the C-terminal domain of Lsd19 catalyzes the intriguing anti-Baldwin cyclization. We propose a general mechanism for epoxide selection by ionophore polyether epoxide hydrolases.

Epoxide hydrolase-lasalocid a structure provides mechanistic insight into polyether natural product biosynthesis.,Wong FT, Hotta K, Chen X, Fang M, Watanabe K, Kim CY J Am Chem Soc. 2015 Jan 14;137(1):86-9. doi: 10.1021/ja511374k. Epub 2014 Dec 31. PMID:25535803^[5]

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

References

↑ Shichijo Y, Migita A, Oguri H, Watanabe M, Tokiwano T, Watanabe K, Oikawa H. Epoxide hydrolase Lsd19 for polyether formation in the biosynthesis of lasalocid A: direct experimental evidence on polyene-polyepoxide hypothesis in polyether biosynthesis. J Am Chem Soc. 2008 Sep 17;130(37):12230-1. doi: 10.1021/ja8040543. Epub 2008 Aug, 19. PMID:18710235 doi:http://dx.doi.org/10.1021/ja8040543
↑ Smith L, Hong H, Spencer JB, Leadlay PF. Analysis of specific mutants in the lasalocid gene cluster: evidence for enzymatic catalysis of a disfavoured polyether ring closure. Chembiochem. 2008 Dec 15;9(18):2967-75. doi: 10.1002/cbic.200800585. PMID:19025863 doi:http://dx.doi.org/10.1002/cbic.200800585
↑ Matsuura Y, Shichijo Y, Minami A, Migita A, Oguri H, Watanabe M, Tokiwano T, Watanabe K, Oikawa H. Intriguing substrate tolerance of epoxide hydrolase Lsd19 involved in biosynthesis of the ionophore antibiotic lasalocid A. Org Lett. 2010 May 21;12(10):2226-9. doi: 10.1021/ol100541e. PMID:20394359 doi:http://dx.doi.org/10.1021/ol100541e
↑ Minami A, Migita A, Inada D, Hotta K, Watanabe K, Oguri H, Oikawa H. Enzymatic epoxide-opening cascades catalyzed by a pair of epoxide hydrolases in the ionophore polyether biosynthesis. Org Lett. 2011 Apr 1;13(7):1638-41. doi: 10.1021/ol200100e. Epub 2011 Mar 4. PMID:21375229 doi:http://dx.doi.org/10.1021/ol200100e
↑ Wong FT, Hotta K, Chen X, Fang M, Watanabe K, Kim CY. Epoxide hydrolase-lasalocid a structure provides mechanistic insight into polyether natural product biosynthesis. J Am Chem Soc. 2015 Jan 14;137(1):86-9. doi: 10.1021/ja511374k. Epub 2014 Dec 31. PMID:25535803 doi:http://dx.doi.org/10.1021/ja511374k

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/4rzm"

@@ Line 1: / Line 1: @@
-'''Unreleased structure'''
+==Crystal structure of the Lsd19-lasalocid A complex==
+<StructureSection load='4rzm' size='340' side='right' caption='[[4rzm]], [[Resolution|resolution]] 2.33&Aring;' scene=''>
+== Structural highlights ==
+<table><tr><td colspan='2'>[[4rzm]] is a 2 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4RZM OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4RZM FirstGlance]. <br>
+</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=CL:CHLORIDE+ION'>CL</scene>, <scene name='pdbligand=FMT:FORMIC+ACID'>FMT</scene>, <scene name='pdbligand=GOL:GLYCEROL'>GOL</scene>, <scene name='pdbligand=LSD:LASALOCID+A'>LSD</scene>, <scene name='pdbligand=NA:SODIUM+ION'>NA</scene></td></tr>
+<tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[3rga|3rga]]</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=4rzm FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4rzm OCA], [http://www.rcsb.org/pdb/explore.do?structureId=4rzm RCSB], [http://www.ebi.ac.uk/pdbsum/4rzm PDBsum]</span></td></tr>
+</table>
+== Function ==
+[[http://www.uniprot.org/uniprot/LSD19_STRLS LSD19_STRLS]] Epoxide hydrolase responsible for the double epoxide-opening cyclization of bisepoxyprelasalocid A to form lasalocid A, a polyether antibiotic. In vitro, accepts various substrate analogs differing in the left segment of lasalocid and epoxide stereochemistry to afford products with excellent regioselectivity.<ref>PMID:18710235</ref> <ref>PMID:19025863</ref> <ref>PMID:20394359</ref> <ref>PMID:21375229</ref>
+<div style="background-color:#fffaf0;">
+== Publication Abstract from PubMed ==
+Biosynthesis of some polyether natural products involves a kinetically disfavored epoxide-opening cyclic ether formation, a reaction termed anti-Baldwin cyclization. One such example is the biosynthesis of lasalocid A, an ionophore antibiotic polyether. During lasalocid A biosynthesis, an epoxide hydrolase, Lsd19, converts the bisepoxy polyketide intermediate into the tetrahydrofuranyl-tetrahydropyran product. We report the crystal structure of Lsd19 in complex with lasalocid A. The structure unambiguously shows that the C-terminal domain of Lsd19 catalyzes the intriguing anti-Baldwin cyclization. We propose a general mechanism for epoxide selection by ionophore polyether epoxide hydrolases.
-The entry 4rzm is ON HOLD
+Epoxide hydrolase-lasalocid a structure provides mechanistic insight into polyether natural product biosynthesis.,Wong FT, Hotta K, Chen X, Fang M, Watanabe K, Kim CY J Am Chem Soc. 2015 Jan 14;137(1):86-9. doi: 10.1021/ja511374k. Epub 2014 Dec 31. PMID:25535803<ref>PMID:25535803</ref>
-Authors: Mathews, I.I., Hotta, K., Chen, X., Kim, C.-Y.
+From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
+</div>
-Description: Crystal structure of the Lsd19-lasalocid A complex
+== References ==
-[[Category: Unreleased Structures]]
+<references/>
+__TOC__
+</StructureSection>
+[[Category: Chen, X]]
 [[Category: Hotta, K]]
-[[Category: Mathews, I.I]]
+[[Category: Kim, C Y]]
-[[Category: Chen, X]]
+[[Category: Mathews, I I]]
-[[Category: Kim, C.-Y]]
+[[Category: Epoxide-opening cyclic ether formation]]
+[[Category: Isomerase]]
+[[Category: Isomerization]]
+[[Category: Ntf2-like fold]]

4rzm

From Proteopedia

Revision as of 16:46, 21 January 2015

Crystal structure of the Lsd19-lasalocid A complex

Structural highlights

Function

Publication Abstract from PubMed

References

Contents

Proteopedia Page Contributors and Editors (what is this?)

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