Stereochemistry of enzymatic transformations of (+)β- and (-)β-HBCD with LinA2--a HCH-degrading bacterial enzyme of Sphingobium indicum B90A
Heeb, NV; Wyss, SA; Geueke, B; Fleischmann, T; Kohler, HP; Bernd Schweizer, W; Moor, H; Lienemann, P
HERO ID
2902364
Reference Type
Journal Article
Year
2015
Language
English
PMID
| HERO ID | 2902364 |
|---|---|
| In Press | No |
| Year | 2015 |
| Title | Stereochemistry of enzymatic transformations of (+)β- and (-)β-HBCD with LinA2--a HCH-degrading bacterial enzyme of Sphingobium indicum B90A |
| Authors | Heeb, NV; Wyss, SA; Geueke, B; Fleischmann, T; Kohler, HP; Bernd Schweizer, W; Moor, H; Lienemann, P |
| Journal | Chemosphere |
| Volume | 122 |
| Page Numbers | 70-78 |
| Abstract | LinA2, a bacterial enzyme expressed in various Sphingomonadaceae, catalyzes the elimination of HCl from hexachlorocyclohexanes (HCHs) and, as discussed here, the release of HBr from certain hexabromocyclododecanes (HBCDs). Both classes of compounds are persistent organic pollutants now regulated under the Stockholm Convention. LinA2 selectively catalyzes the transformation of β-HBCDs; other stereoisomers like α-, γ-, and δ-HBCDs are not converted. The transformation of (-)β-HBCD is considerably faster than that of its enantiomer. Here, we present the XRD crystal structure of 1E,5S,6S,9R,10S-pentabromocyclododecene (PBCDE) and demonstrate that its enantiomer with the 1E,5R,6R,9S,10R-configuration is the only metabolite formed during LinA2-catalyzed dehydrobromination of (-)β-HBCD. Formation of this product can be rationalized by HBr elimination at C5 and C6. A reasonable enzyme-substrate complex with the catalytic dyad His-73 and Asp-25 approaching the hydrogen at C6 and a cationic pocket of Lys-20, Try-42 and Arg-129 binding the leaving bromine at C5 was found from in silico docking experiments. A second PBCDE of yet unknown configuration was obtained from (+)β-HBCD. We predicted its stereochemistry to be 1E,5S,6S,9S,10R-PBCDE from docking experiments. The enzyme-substrate complex obtained from LinA2 and an activated conformation of (+)β-HBCD allows the HBr elimination at C9 and C10 leading to the predicted product. Both modeled enzyme-substrate complexes are in line with 1,2-diaxial HBr eliminations. In conclusion, LinA2, a bacterial enzyme of the HCH-degrading strain Sphingobium indicum B90A was able to stereoselectively convert β-HBCDs. Configurations of both PBCDE metabolites were predicted by molecular docking experiments and confirmed in one case by XRD data. |
| Doi | 10.1016/j.chemosphere.2014.11.008 |
| Pmid | 25434265 |
| Wosid | WOS:000348952300010 |
| Is Certified Translation | No |
| Dupe Override | No |
| Is Public | Yes |
| Language Text | English |