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| | <StructureSection load='2rez' size='340' side='right'caption='[[2rez]], [[Resolution|resolution]] 1.95Å' scene=''> | | <StructureSection load='2rez' size='340' side='right'caption='[[2rez]], [[Resolution|resolution]] 1.95Å' scene=''> |
| | == Structural highlights == | | == Structural highlights == |
| - | <table><tr><td colspan='2'>[[2rez]] is a 1 chain structure with sequence from [https://en.wikipedia.org/wiki/"actinomyces_glaucescens"_preobrazhenskaya_in_gauze_et_al._1957 "actinomyces glaucescens" preobrazhenskaya in gauze et al. 1957]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2REZ OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=2REZ FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[2rez]] is a 1 chain structure with sequence from [https://en.wikipedia.org/wiki/Streptomyces_glaucescens Streptomyces glaucescens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2REZ OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=2REZ FirstGlance]. <br> |
| - | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=ACT:ACETATE+ION'>ACT</scene>, <scene name='pdbligand=IOD:IODIDE+ION'>IOD</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]] 1.95Å</td></tr> |
| - | <tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat"><div style='overflow: auto; max-height: 3em;'>[[2rer|2rer]], [[2res|2res]]</div></td></tr> | + | <tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=ACT:ACETATE+ION'>ACT</scene>, <scene name='pdbligand=IOD:IODIDE+ION'>IOD</scene></td></tr> |
| - | <tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">tcmN ([https://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=1907 "Actinomyces glaucescens" Preobrazhenskaya in Gauze et al. 1957])</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=2rez FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2rez OCA], [https://pdbe.org/2rez PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=2rez RCSB], [https://www.ebi.ac.uk/pdbsum/2rez PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=2rez ProSAT]</span></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=2rez FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2rez OCA], [https://pdbe.org/2rez PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=2rez RCSB], [https://www.ebi.ac.uk/pdbsum/2rez PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=2rez ProSAT]</span></td></tr> |
| | </table> | | </table> |
| | == Function == | | == Function == |
| - | [[https://www.uniprot.org/uniprot/TCMN_STRGA TCMN_STRGA]] The N-terminal domain enhances the formation of an early, partially cyclized intermediate, while the C-terminal domain catalyzes the 3-O-methylation of one or more later intermediates in the biosynthetic pathway. Catalyzes the methylation of tetracenomycin D3 (Tcm D3) to yield Tcm B3. Catalyzes as well the following side reactions: methylation of 8-O-methyl-Tcm D3 to yield Tcm E; and of 9-carboxymethyl-Tcm B3 to yield Tcm A2.
| + | [https://www.uniprot.org/uniprot/TCMN_STRGA TCMN_STRGA] The N-terminal domain enhances the formation of an early, partially cyclized intermediate, while the C-terminal domain catalyzes the 3-O-methylation of one or more later intermediates in the biosynthetic pathway. Catalyzes the methylation of tetracenomycin D3 (Tcm D3) to yield Tcm B3. Catalyzes as well the following side reactions: methylation of 8-O-methyl-Tcm D3 to yield Tcm E; and of 9-carboxymethyl-Tcm B3 to yield Tcm A2. |
| | == Evolutionary Conservation == | | == Evolutionary Conservation == |
| | [[Image:Consurf_key_small.gif|200px|right]] | | [[Image:Consurf_key_small.gif|200px|right]] |
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| | __TOC__ | | __TOC__ |
| | </StructureSection> | | </StructureSection> |
| - | [[Category: Actinomyces glaucescens preobrazhenskaya in gauze et al. 1957]] | |
| | [[Category: Large Structures]] | | [[Category: Large Structures]] |
| - | [[Category: Ames, B D]] | + | [[Category: Streptomyces glaucescens]] |
| - | [[Category: Tsai, S C]] | + | [[Category: Ames BD]] |
| - | [[Category: Antibiotic biosynthesis]] | + | [[Category: Tsai SC]] |
| - | [[Category: Aromatase]]
| + | |
| - | [[Category: Biosynthetic protein]]
| + | |
| - | [[Category: Cyclase]]
| + | |
| - | [[Category: Dehydratase]]
| + | |
| - | [[Category: Double-hot-dog]]
| + | |
| - | [[Category: Helix-grip]]
| + | |
| - | [[Category: Methyltransferase]]
| + | |
| - | [[Category: Multifunctional enzyme]]
| + | |
| - | [[Category: Polyketide]]
| + | |
| - | [[Category: Tetracenomycin]]
| + | |
| - | [[Category: Transferase]]
| + | |
| Structural highlights
Function
TCMN_STRGA The N-terminal domain enhances the formation of an early, partially cyclized intermediate, while the C-terminal domain catalyzes the 3-O-methylation of one or more later intermediates in the biosynthetic pathway. Catalyzes the methylation of tetracenomycin D3 (Tcm D3) to yield Tcm B3. Catalyzes as well the following side reactions: methylation of 8-O-methyl-Tcm D3 to yield Tcm E; and of 9-carboxymethyl-Tcm B3 to yield Tcm A2.
Evolutionary Conservation
Check, as determined by ConSurfDB. You may read the explanation of the method and the full data available from ConSurf.
Publication Abstract from PubMed
Polyketides are a class of natural products with highly diverse chemical structures and pharmaceutical activities. Polyketide cyclization, promoted by the aromatase/cyclase (ARO/CYC), helps diversify aromatic polyketides. How the ARO/CYC promotes highly specific cyclization is not well understood because of the lack of a first-ring ARO/CYC structure. The 1.9 A crystal structure of Tcm ARO/CYC reveals that the enzyme belongs to the Bet v1-like superfamily (or STAR domain family) with a helix-grip fold, and contains a highly conserved interior pocket. Docking, mutagenesis, and an in vivo assay show that the size, shape, and composition of the pocket are important to orient and specifically fold the polyketide chain for C9-C14 first-ring and C7-C16 second-ring cyclizations. Two pocket residues, R69 and Y35, were found to be essential for promoting first- and second-ring cyclization specificity. Different pocket residue mutations affected the polyketide product distribution. A mechanism is proposed based on the structure-mutation-docking results. These results strongly suggest that the regiospecific cyclizations of the first two rings and subsequent aromatizations take place in the interior pocket. The chemical insights gleaned from this work pave the foundation toward defining the molecular rules for the ARO/CYC cyclization specificity, whose rational control will be important for future endeavors in the engineered biosynthesis of novel anticancer and antibiotic aromatic polyketides.
Crystal structure and functional analysis of tetracenomycin ARO/CYC: implications for cyclization specificity of aromatic polyketides.,Ames BD, Korman TP, Zhang W, Smith P, Vu T, Tang Y, Tsai SC Proc Natl Acad Sci U S A. 2008 Apr 8;105(14):5349-54. Epub 2008 Apr 3. PMID:18388203[1]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
References
- ↑ Ames BD, Korman TP, Zhang W, Smith P, Vu T, Tang Y, Tsai SC. Crystal structure and functional analysis of tetracenomycin ARO/CYC: implications for cyclization specificity of aromatic polyketides. Proc Natl Acad Sci U S A. 2008 Apr 8;105(14):5349-54. Epub 2008 Apr 3. PMID:18388203
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