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4omg

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Revision as of 07:32, 25 January 2023

Crystal structure of the bacterial diterpene cyclase COTB2

Structural highlights

4omg is a 2 chain structure with sequence from Streptomyces melanosporofaciens. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Ligands:	,
Resources:	FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Function

COTB2_STRMJ Catalyzes the cyclization of the linear isoprenoid intermediate geranylgeranyl diphosphate to tricycclic cyclooctat-9-en-7-ol in the cyclooctatin biosynthesis pathway. Cyclooctatin is a potent inhibitor of lysophospholipase.^[1] ^[2]

Publication Abstract from PubMed

Sesquiterpenes and diterpenes are a diverse class of secondary metabolites that are predominantly derived from plants and some prokaryotes. The properties of these natural products encompass antitumor, antibiotic and even insecticidal activities. Therefore, they are interesting commercial targets for the chemical and pharmaceutical industries. Owing to their structural complexity, these compounds are more efficiently accessed by metabolic engineering of microbial systems than by chemical synthesis. This work presents the first crystal structure of a bacterial diterpene cyclase, CotB2 from the soil bacterium Streptomyces melanosporofaciens, at 1.64 A resolution. CotB2 is a diterpene cyclase that catalyzes the cyclization of the linear geranylgeranyl diphosphate to the tricyclic cyclooctat-9-en-7-ol. The subsequent oxidation of cyclooctat-9-en-7-ol by two cytochrome P450 monooxygenases leads to bioactive cyclooctatin. Plasticity residues that decorate the active site of CotB2 have been mutated, resulting in alternative monocyclic, dicyclic and tricyclic compounds that show bioactivity. These new compounds shed new light on diterpene cyclase reaction mechanisms. Furthermore, the product of mutant CotB2(W288G) produced the new antibiotic compound (1R,3E,7E,11S,12S)-3,7,18-dolabellatriene, which acts specifically against multidrug-resistant Staphylococcus aureus. This opens a sustainable route for the industrial-scale production of this bioactive compound.

The first structure of a bacterial diterpene cyclase: CotB2.,Janke R, Gorner C, Hirte M, Bruck T, Loll B Acta Crystallogr D Biol Crystallogr. 2014 Jun;70(Pt 6):1528-37. doi:, 10.1107/S1399004714005513. Epub 2014 May 23. PMID:24914964^[3]

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

References

↑ Kim SY, Zhao P, Igarashi M, Sawa R, Tomita T, Nishiyama M, Kuzuyama T. Cloning and heterologous expression of the cyclooctatin biosynthetic gene cluster afford a diterpene cyclase and two p450 hydroxylases. Chem Biol. 2009 Jul 31;16(7):736-43. doi: 10.1016/j.chembiol.2009.06.007. PMID:19635410 doi:http://dx.doi.org/10.1016/j.chembiol.2009.06.007
↑ Janke R, Gorner C, Hirte M, Bruck T, Loll B. The first structure of a bacterial diterpene cyclase: CotB2. Acta Crystallogr D Biol Crystallogr. 2014 Jun;70(Pt 6):1528-37. doi:, 10.1107/S1399004714005513. Epub 2014 May 23. PMID:24914964 doi:http://dx.doi.org/10.1107/S1399004714005513
↑ Janke R, Gorner C, Hirte M, Bruck T, Loll B. The first structure of a bacterial diterpene cyclase: CotB2. Acta Crystallogr D Biol Crystallogr. 2014 Jun;70(Pt 6):1528-37. doi:, 10.1107/S1399004714005513. Epub 2014 May 23. PMID:24914964 doi:http://dx.doi.org/10.1107/S1399004714005513

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/4omg"

@@ Line 3: / Line 3: @@
 <StructureSection load='4omg' size='340' side='right'caption='[[4omg]], [[Resolution|resolution]] 1.64&Aring;' scene=''>
 == Structural highlights ==
-<table><tr><td colspan='2'>[[4omg]] is a 2 chain structure with sequence from [http://en.wikipedia.org/wiki/Atcc_25473 Atcc 25473]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4OMG OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4OMG FirstGlance]. <br>
+<table><tr><td colspan='2'>[[4omg]] is a 2 chain structure with sequence from [https://en.wikipedia.org/wiki/Streptomyces_melanosporofaciens Streptomyces melanosporofaciens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4OMG OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=4OMG FirstGlance]. <br>
-</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=CXS:3-CYCLOHEXYL-1-PROPYLSULFONIC+ACID'>CXS</scene>, <scene name='pdbligand=NA:SODIUM+ION'>NA</scene></td></tr>
+</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=CXS:3-CYCLOHEXYL-1-PROPYLSULFONIC+ACID'>CXS</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">[[4omh|4omh]], [[4omi|4omi]]</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=4omg FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4omg OCA], [https://pdbe.org/4omg PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=4omg RCSB], [https://www.ebi.ac.uk/pdbsum/4omg PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=4omg 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=4omg FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4omg OCA], [http://pdbe.org/4omg PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=4omg RCSB], [http://www.ebi.ac.uk/pdbsum/4omg PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=4omg ProSAT]</span></td></tr>
 </table>
+== Function ==
+[https://www.uniprot.org/uniprot/COTB2_STRMJ COTB2_STRMJ] Catalyzes the cyclization of the linear isoprenoid intermediate geranylgeranyl diphosphate to tricycclic cyclooctat-9-en-7-ol in the cyclooctatin biosynthesis pathway. Cyclooctatin is a potent inhibitor of lysophospholipase.<ref>PMID:19635410</ref> <ref>PMID:24914964</ref>
 <div style="background-color:#fffaf0;">
 == Publication Abstract from PubMed ==
@@ Line 21: / Line 22: @@
 __TOC__
 </StructureSection>
-[[Category: Atcc 25473]]
 [[Category: Large Structures]]
-[[Category: Brueck, T]]
+[[Category: Streptomyces melanosporofaciens]]
-[[Category: Goerner, C]]
+[[Category: Brueck T]]
-[[Category: Hirte, M]]
+[[Category: Goerner C]]
-[[Category: Janke, R]]
+[[Category: Hirte M]]
-[[Category: Loll, B]]
+[[Category: Janke R]]
-[[Category: Class i terpene cyclase fold]]
+[[Category: Loll B]]
-[[Category: Geranylgeranyl diphophate]]
-[[Category: Lyase]]
-[[Category: Terpene cyclase]]

4omg

From Proteopedia

Revision as of 07:32, 25 January 2023

Crystal structure of the bacterial diterpene cyclase COTB2

Structural highlights

Function

Publication Abstract from PubMed

References

Contents

Proteopedia Page Contributors and Editors (what is this?)

Views

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