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- Name help_outline L-tryptophan Identifier CHEBI:57912 Charge 0 Formula C11H12N2O2 InChIKeyhelp_outline QIVBCDIJIAJPQS-VIFPVBQESA-N SMILEShelp_outline [NH3+][C@@H](Cc1c[nH]c2ccccc12)C([O-])=O 2D coordinates Mol file for the small molecule Search links Involved in 57 reaction(s) Find molecules that contain or resemble this structure Find proteins in UniProtKB for this molecule
- Name help_outline FADH2 Identifier CHEBI:58307 Charge -2 Formula C27H33N9O15P2 InChIKeyhelp_outline YPZRHBJKEMOYQH-UYBVJOGSSA-L SMILEShelp_outline Cc1cc2Nc3c([nH]c(=O)[nH]c3=O)N(C[C@H](O)[C@H](O)[C@H](O)COP([O-])(=O)OP([O-])(=O)OC[C@H]3O[C@H]([C@H](O)[C@@H]3O)n3cnc4c(N)ncnc34)c2cc1C 2D coordinates Mol file for the small molecule Search links Involved in 163 reaction(s) Find molecules that contain or resemble this structure Find proteins in UniProtKB for this molecule
- Name help_outline chloride Identifier CHEBI:17996 (Beilstein: 3587171; CAS: 16887-00-6) help_outline Charge -1 Formula Cl InChIKeyhelp_outline VEXZGXHMUGYJMC-UHFFFAOYSA-M SMILEShelp_outline [Cl-] 2D coordinates Mol file for the small molecule Search links Involved in 139 reaction(s) Find molecules that contain or resemble this structure Find proteins in UniProtKB for this molecule
- Name help_outline O2 Identifier CHEBI:15379 (CAS: 7782-44-7) help_outline Charge 0 Formula O2 InChIKeyhelp_outline MYMOFIZGZYHOMD-UHFFFAOYSA-N SMILEShelp_outline O=O 2D coordinates Mol file for the small molecule Search links Involved in 2,727 reaction(s) Find molecules that contain or resemble this structure Find proteins in UniProtKB for this molecule
- Name help_outline 7-chloro-L-tryptophan Identifier CHEBI:58713 Charge 0 Formula C11H11ClN2O2 InChIKeyhelp_outline DMQFGLHRDFQKNR-VIFPVBQESA-N SMILEShelp_outline [NH3+][C@@H](Cc1c[nH]c2c(Cl)cccc12)C([O-])=O 2D coordinates Mol file for the small molecule Search links Involved in 4 reaction(s) Find molecules that contain or resemble this structure Find proteins in UniProtKB for this molecule
- Name help_outline FAD Identifier CHEBI:57692 Charge -3 Formula C27H30N9O15P2 InChIKeyhelp_outline IMGVNJNCCGXBHD-UYBVJOGSSA-K SMILEShelp_outline Cc1cc2nc3c(nc(=O)[n-]c3=O)n(C[C@H](O)[C@H](O)[C@H](O)COP([O-])(=O)OP([O-])(=O)OC[C@H]3O[C@H]([C@H](O)[C@@H]3O)n3cnc4c(N)ncnc34)c2cc1C 2D coordinates Mol file for the small molecule Search links Involved in 172 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
Cross-references
| RHEA:26494 | RHEA:26495 | RHEA:26496 | RHEA:26497 | |
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| Reaction direction help_outline | undefined | left-to-right | right-to-left | bidirectional |
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Publications
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Crystallization and X-ray diffraction of a halogenating enzyme, tryptophan 7-halogenase, from Pseudomonas fluorescens.
Dong C., Kotzsch A., Dorward M., van Pee K.H., Naismith J.H.
Chlorination of natural products is often required for their biological activity; notable examples include vancomycin, the last-ditch antibiotic. It is now known that many chlorinated natural products are made not by haloperoxidases, but by FADH2-dependent halogenases. The mechanism of the flavin- ... >> More
Chlorination of natural products is often required for their biological activity; notable examples include vancomycin, the last-ditch antibiotic. It is now known that many chlorinated natural products are made not by haloperoxidases, but by FADH2-dependent halogenases. The mechanism of the flavin-containing enzymes is obscure and there are no structural data. Here, crystals of PrnA (tryptophan 7-halogenase), an enzyme that regioselectively chlorinates tryptophan, cocrystallized with tryptophan and FAD are reported. The crystals belong to the tetragonal space group P4(3)2(1)2 or P4(1)2(1)2, with unit-cell parameters a = b = 67.8, c = 276.9 A. A data set to 1.8 A with 93% completeness and an Rmerge of 7.1% has been collected from a single flash-cooled crystal. A method for incorporating selenomethionine in a Pseudomonas fluorescens expression system also is reported. << Less
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The structure of flavin-dependent tryptophan 7-halogenase RebH.
Bitto E., Huang Y., Bingman C.A., Singh S., Thorson J.S., Phillips G.N.
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Robust in vitro activity of RebF and RebH, a two-component reductase/halogenase, generating 7-chlorotryptophan during rebeccamycin biosynthesis.
Yeh E., Garneau S., Walsh C.T.
The indolocarbazole antitumor agent rebeccamycin is modified by chlorine atoms on each of two indole moieties of the aglycone scaffold. These halogens are incorporated during the initial step of its biosynthesis from conversion of L-Trp to 7-chlorotryptophan. Two genes in the biosynthetic cluster, ... >> More
The indolocarbazole antitumor agent rebeccamycin is modified by chlorine atoms on each of two indole moieties of the aglycone scaffold. These halogens are incorporated during the initial step of its biosynthesis from conversion of L-Trp to 7-chlorotryptophan. Two genes in the biosynthetic cluster, rebF and rebH, are predicted to encode the flavin reductase and halogenase components of an FADH2-dependent halogenase, a class of enzymes involved in the biosynthesis of numerous halogenated natural products. Here, we report that, in the presence of O2, chloride ion, and L-Trp as cosubstrates, purified RebH displays robust regiospecific halogenating activity to generate 7-chlorotryptophan over at least 50 catalytic cycles. Halogenation by RebH required the addition of RebF, which catalyzes the NADH-dependent reduction of FAD to provide FADH2 for the halogenase. Maximal rates were achieved at a RebF/RebH ratio of 3:1. In air-saturated solutions, a k(cat) of 1.4 min(-1) was observed for the RebF/RebH system but increased at least 10-fold in low-pO2 conditions. RebH was also able to use bromide ions to generate monobrominated Trp. The demonstration of robust chlorinating activity by RebF/RebH sets up this system for the probing of mechanistic questions regarding this intriguing class of enzymes. << Less
Proc. Natl. Acad. Sci. U.S.A. 102:3960-3965(2005) [PubMed] [EuropePMC]