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- Name help_outline ent-copalyl diphosphate Identifier CHEBI:58553 Charge -3 Formula C20H33O7P2 InChIKeyhelp_outline JCAIWDXKLCEQEO-PGHZQYBFSA-K SMILEShelp_outline [C@@H]1(CC/C(/C)=C/COP(OP(=O)([O-])[O-])(=O)[O-])C(=C)CC[C@]2([C@@]1(C)CCCC2(C)C)[H] 2D coordinates Mol file for the small molecule Search links Involved in 16 reaction(s) Find molecules that contain or resemble this structure Find proteins in UniProtKB for this molecule
- Name help_outline H2O Identifier CHEBI:15377 (CAS: 7732-18-5) help_outline Charge 0 Formula H2O InChIKeyhelp_outline XLYOFNOQVPJJNP-UHFFFAOYSA-N SMILEShelp_outline [H]O[H] 2D coordinates Mol file for the small molecule Search links Involved in 6,264 reaction(s) Find molecules that contain or resemble this structure Find proteins in UniProtKB for this molecule
- Name help_outline (−)-ent-copalol Identifier CHEBI:76950 Charge 0 Formula C20H34O InChIKeyhelp_outline NERNKRPBSOBEHC-PGHZQYBFSA-N SMILEShelp_outline C\C(CC[C@@H]1C(=C)CC[C@@H]2C(C)(C)CCC[C@@]12C)=C/CO 2D coordinates Mol file for the small molecule Search links Involved in 1 reaction(s) Find molecules that contain or resemble this structure Find proteins in UniProtKB for this molecule
- Name help_outline diphosphate Identifier CHEBI:33019 (Beilstein: 185088) help_outline Charge -3 Formula HO7P2 InChIKeyhelp_outline XPPKVPWEQAFLFU-UHFFFAOYSA-K SMILEShelp_outline OP([O-])(=O)OP([O-])([O-])=O 2D coordinates Mol file for the small molecule Search links Involved in 1,139 reaction(s) Find molecules that contain or resemble this structure Find proteins in UniProtKB for this molecule
Cross-references
| RHEA:40019 | RHEA:40020 | RHEA:40021 | RHEA:40022 | |
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| Reaction direction help_outline | undefined | left-to-right | right-to-left | bidirectional |
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| MetaCyc help_outline |
Publications
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Substrate specificity of Rv3378c, an enzyme from Mycobacterium tuberculosis, and the inhibitory activity of the bicyclic diterpenoids against macrophage phagocytosis.
Hoshino T., Nakano C., Ootsuka T., Shinohara Y., Hara T.
The Rv3378c gene product from Mycobacterium tuberculosis encodes a diterpene synthase to produce tuberculosinol (3), 13R-isotuberculosinol (4a), and 13S-isotuberculosinol (4b) from tuberculosinyl diphosphate (2). The product distribution ratios are 1 : 1 for 3 to 4 and 1 : 3 for 4a to 4b. The subs ... >> More
The Rv3378c gene product from Mycobacterium tuberculosis encodes a diterpene synthase to produce tuberculosinol (3), 13R-isotuberculosinol (4a), and 13S-isotuberculosinol (4b) from tuberculosinyl diphosphate (2). The product distribution ratios are 1 : 1 for 3 to 4 and 1 : 3 for 4a to 4b. The substrate specificity of the Rv3378c-encoded enzyme was examined. The 3 labdadienyl diphosphates, copalyl diphosphate (CDP) (7), ent-CDP (8), and syn-CDP (9), underwent the conversion reaction, with good yields (67-78%). Copalol (23) and manool (24) were produced from 7, ent-copalol (25) and ent-manool (26) from 8, and syn-copalol (27) and vitexifolin A (28) from 9. The ratio of 23 to 24 was 40 : 27, that of 25:26 was 22 : 50, and that of 27:28 was 16 : 62. Analysis on a GC-MS chromatograph equipped with a chiral column revealed that 24, 26, and 28 consisted of a mixture of 13R-(a) and 13S-stereoisomers (b) in the following ratio: ca. 1 : 1 for 24a to 24b, ca. 1 : 5 for 26a to 26b, and ca. 1 : 19 for 28a to 28b. The structures of these products indicate that the reactions of the 3 CDPs proceeded in the same fashion as that of 2. This is the first report on the enzymatic synthesis of natural diterpenes manool, ent-manool, and vitexifolin A. Both Rv3377c and Rv3378c genes are found in virulent Mycobacterium species, but not in avirulent species. We found that 3 and 4 inhibited the phagocytosis of opsonized zymosan particles by human macrophage-like cells. Interestingly, the inhibitory activity was synergistically increased by the coexistence of 3 and 4b. Other labdane-related diterpenes, 13-16 and 23-28, had little or no inhibitory activity. This synergistic inhibition by 3 and 4 may provide further advantage to the impairment of phagocyte function, which might contribute to pathogenicity of M. tuberculosis. << Less
Org. Biomol. Chem. 9:2156-2165(2011) [PubMed] [EuropePMC]
This publication is cited by 9 other entries.