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| | ==Crystal structure of CotB2 (apo form) from Streptomyces melanosporofaciens== | | ==Crystal structure of CotB2 (apo form) from Streptomyces melanosporofaciens== |
| - | <StructureSection load='5guc' size='340' side='right' caption='[[5guc]], [[Resolution|resolution]] 1.80Å' scene=''> | + | <StructureSection load='5guc' size='340' side='right'caption='[[5guc]], [[Resolution|resolution]] 1.80Å' scene=''> |
| | == Structural highlights == | | == Structural highlights == |
| - | <table><tr><td colspan='2'>[[5guc]] 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=5GUC OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=5GUC FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[5guc]] 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=5GUC OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=5GUC FirstGlance]. <br> |
| - | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=FMT:FORMIC+ACID'>FMT</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]] 1.8Å</td></tr> |
| - | <tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[5gue|5gue]]</td></tr>
| + | <tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=FMT:FORMIC+ACID'>FMT</scene></td></tr> |
| - | <tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">CotB2 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=67327 ATCC 25473])</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=5guc FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5guc OCA], [https://pdbe.org/5guc PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=5guc RCSB], [https://www.ebi.ac.uk/pdbsum/5guc PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=5guc ProSAT]</span></td></tr> |
| - | <tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[http://en.wikipedia.org/wiki/Lyase Lyase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=4.2.3.146 4.2.3.146] </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=5guc FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5guc OCA], [http://pdbe.org/5guc PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=5guc RCSB], [http://www.ebi.ac.uk/pdbsum/5guc PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=5guc ProSAT]</span></td></tr> | + | |
| | </table> | | </table> |
| | == Function == | | == Function == |
| - | [[http://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> | + | [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;"> | | <div style="background-color:#fffaf0;"> |
| | == Publication Abstract from PubMed == | | == Publication Abstract from PubMed == |
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| | __TOC__ | | __TOC__ |
| | </StructureSection> | | </StructureSection> |
| - | [[Category: Atcc 25473]] | + | [[Category: Large Structures]] |
| - | [[Category: Lyase]] | + | [[Category: Streptomyces melanosporofaciens]] |
| - | [[Category: Kim, S Y]] | + | [[Category: Kim S-Y]] |
| - | [[Category: Kuzuyama, T]] | + | [[Category: Kuzuyama T]] |
| - | [[Category: Nishiyama, M]] | + | [[Category: Nishiyama M]] |
| - | [[Category: Ozaki, T]] | + | [[Category: Ozaki T]] |
| - | [[Category: Tomita, T]] | + | [[Category: Tomita T]] |
| - | [[Category: Yoshida, A]] | + | [[Category: Yoshida A]] |
| - | [[Category: Biosynthetic protein]]
| + | |
| - | [[Category: Diterpene cyclase]]
| + | |
| - | [[Category: Terpene cyclase fold]]
| + | |
| Structural highlights
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
The diterpene cyclase CotB2 catalyzes the cyclization of geranylgeranyl diphosphate (GGPP) to the tricyclic cyclooctat-9-en-7-ol, which is characterized by a 5-8-5-fused ring skeleton. We have previously proposed a cyclization cascade involving a unique carbon-carbon bond rearrangement combined with multiple hydride shifts, all occurring at a single active site. Here, we report the first high-resolution X-ray crystal structure of CotB2 with bound substrate analog geranylgeranyl thiodiphosphate (GGSPP). In the GGSPP-bound form, GGSPP folds into a unique S-shaped conformation that probably reflects the substrate-bound state prior to ionization of the substrate GGPP. The folded framework of GGSPP is surrounded by hydrophobic residues and several aromatic and asparagine residues that are well-positioned to stabilize a series of reactive carbocation intermediates through a combination of cation-pi and dipole charge interactions. The combined crystal structures and mutagenesis-based biochemical assays provide a structural basis for exquisite control of ring formation and stereochemistry during CotB2 catalysis.
Structural Insights into the CotB2-Catalyzed Cyclization of Geranylgeranyl Diphosphate to the Diterpene Cyclooctat-9-en-7-ol.,Tomita T, Kim SY, Teramoto K, Meguro A, Ozaki T, Yoshida A, Motoyoshi Y, Mori N, Ishigami K, Watanabe H, Nishiyama M, Kuzuyama T ACS Chem Biol. 2017 Jun 16;12(6):1621-1628. doi: 10.1021/acschembio.7b00154. Epub, 2017 May 2. PMID:28463490[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
- ↑ Tomita T, Kim SY, Teramoto K, Meguro A, Ozaki T, Yoshida A, Motoyoshi Y, Mori N, Ishigami K, Watanabe H, Nishiyama M, Kuzuyama T. Structural Insights into the CotB2-Catalyzed Cyclization of Geranylgeranyl Diphosphate to the Diterpene Cyclooctat-9-en-7-ol. ACS Chem Biol. 2017 Jun 16;12(6):1621-1628. doi: 10.1021/acschembio.7b00154. Epub, 2017 May 2. PMID:28463490 doi:http://dx.doi.org/10.1021/acschembio.7b00154
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