3‐Sulfinopropionyl‐coenzyme A (3SP‐CoA) desulfinase from Advenella mimigardefordensis DPN7T: crystal structure and function of a desulfinase with an acyl‐CoA dehydrogenase fold. (1st June 2015)

• Record Type: Journal Article
• Authors: Schürmann, Marc; Meijers, Rob; Schneider, Thomas R.; Steinbüchel, Alexander; Cianci, Michele
• Is Part Of: Acta crystallographica. Volume 71:Part 6(2015:Jun.)
• Page Start: 1360
• Page End: 1372
• Publication Date: 2015-06-01
• Subjects: Biomolecules -- Structure -- Periodicals; Physical biochemistry -- Periodicals; X-ray crystallography -- Periodicals; Crystallography -- Periodicals; 572
• DOI: 10.1107/S1399004715006616
• Languages: English
• ISSNs: 0907-4449

Abstract

<abstract abstract-type="main" xml:lang="en"> <title> <x xml:space="preserve">Abstract</x> </title> <p>3‐Sulfinopropionyl‐coenzyme A (3SP‐CoA) desulfinase (Acd<sub>DPN7</sub>; EC 3.13.1.4) was identified during investigation of the 3, 3′‐dithiodipropionic acid (DTDP) catabolic pathway in the betaproteobacterium <italic>Advenella mimigardefordensis</italic> strain DPN7<sup>T</sup>. DTDP is an organic disulfide and a precursor for the synthesis of polythioesters (PTEs) in bacteria, and is of interest for biotechnological PTE production. Acd<sub>DPN7</sub> catalyzes sulfur abstraction from 3SP‐CoA, a key step during the catabolism of DTDP. Here, the crystal structures of apo Acd<sub>DPN7</sub> at 1.89 Å resolution and of its complex with the CoA moiety from the substrate analogue succinyl‐CoA at 2.30 Å resolution are presented. The apo structure shows that Acd<sub>DPN7</sub> belongs to the acyl‐CoA dehydrogenase superfamily fold and that it is a tetramer, with each subunit containing one flavin adenine dinucleotide (FAD) molecule. The enzyme does not show any dehydrogenase activity. Dehydrogenase activity would require a catalytic base (Glu or Asp residue) at either position 246 or position 366, where a glutamine and a glycine are instead found, respectively, in this desulfinase. The positioning of CoA in the crystal complex enabled the modelling of a substrate complex containing 3SP‐CoA. This indicates that Arg84 is a key residue in the desulfination reaction. An Arg84Lys mutant showed a complete loss of enzymatic activity, suggesting that the guanidinium group of the arginine is essential for desulfination. Acd<sub>DPN7</sub> is the first desulfinase with an acyl‐CoA dehydrogenase fold to be reported, which underlines the versatility of this enzyme scaffold.</p> </abstract>