2h8z

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spinqualitylabelsall models 2h8z, resolution 1.42Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image

Xenobiotic Reductase A in complex with 8-Hydroxycoumarin

Overview

A continuous evolutionary pressure of the biotic and abiotic world has led, to the development of a diversity of microbial pathways to degrade and, biomineralize aromatic and heteroaromatic compounds. The heterogeneity of, compounds metabolized by bacteria like Pseudomonas putida indicates the, large variety of enzymes necessary to catalyse the required reactions., Quinoline, a N-heterocyclic aromatic compound, can be degraded by microbes, along different pathways. For P. putida 86 quinoline degradation by the, 8-hydroxycoumarin pathway has been described and several intermediates, were identified. To select enzymes catalysing the later stages of the, 8-hydroxycoumarin pathway P. putida 86 was grown with quinoline. The, FMN-containing enzyme xenobiotic reductase A (XenA) was isolated and, analysed for its reactivity with intermediates of the 8-hydroxycoumarin, pathway. XenA catalyses the NADPH-dependent reduction of 8-hydroxycoumarin, and coumarin to produce 8-hydroxy-3,4-dihydrocoumarin and, 3,4-dihydrocoumarin, respectively. Crystallographic analysis of XenA alone, and in complex with the two substrates revealed insights into the, mechanism. XenA shows a dimeric arrangement of two (beta/alpha)(8) barrel, domains each binding one FMN cofactor. High resolution crystal structures, of complexes with 8-hydroxycoumarin and coumarin show different modes of, binding for these molecules in the active site. While coumarin is ideally, positioned for hydride transfer from N-5 of the isoalloxazine ring to C-4, of coumarin, 8-hydroxycoumarin forms a non-productive complex with, oxidised XenA. Orientation of 8-hydroxycoumarin in the active site appears, to be dependent on the electronic state of the flavin. We postulate that, XenA catalyses the last step of the 8-hydroxycoumarin pathway before the, heterocyclic ring is hydrolysed to yield 3-(2,3-dihydroxyphenyl)-propionic, acid. As XenA is also found in P. putida strains unable to degrade, quinoline, it appears to have more than one physiological function and is, an example of how enzymes with low substrate specificity can help to, explain the variety of degradation pathways possible.

About this Structure

2H8Z is a Single protein structure of sequence from Pseudomonas putida with , and as ligands. Full crystallographic information is available from OCA.

Reference

Xenobiotic reductase A in the degradation of quinoline by Pseudomonas putida 86: physiological function, structure and mechanism of 8-hydroxycoumarin reduction., Griese JJ, P Jakob R, Schwarzinger S, Dobbek H, J Mol Biol. 2006 Aug 4;361(1):140-52. Epub 2006 Jun 21. PMID:16822524

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