Identification of an Unusual [2Fe-2S]-Binding Motif in the CDP-6-deoxy-d-glycero-l-threo-4-hexulose-3-dehydrase from Yersinia pseudotuberculosis: Implication for C-3 Deoxygenation in the Biosynthesis of 3,6-Dideoxyhexoses

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Abstract
CDP-6-deoxy-l-threo-d-glycero-4-hexulose-3-dehydrase (E1) catalyzes the C-3 deoxygenation in the biosynthesis of 3,6-dideoxyhexoses in Yersinia pseudotuberculosis. E1 is a pyridoxamine 5‘-phosphate (PMP)-dependent enzyme that also contains a [2Fe-2S] center. This iron−sulfur cluster is catalytically essential, since removal of the [2Fe-2S] center leads to inactive enzyme. To identify the [2Fe-2S] core in E1 and to study the effect of impairing the iron−sulfur cluster on the activity of E1, a series of E1 cysteine mutants were constructed and their catalytic properties were characterized. Our results show that E1 displays a cluster-binding motif (C-X57-C-X1-C-X7-C) that has not been observed previously for [2Fe-2S] proteins. The presence of such an unusual iron−sulfur cluster in E1, along with the replacement of the active site lysine by a histidine residue (H220), reflects a distinct evolutionary path for this enzyme. The cysteine residues (C193, C251, C253, C261) implicated in the binding of the iron−sulfur cluster in E1 are conserved in the sequences of its homologues. It is likely that E1 and its homologues constitute a new subclass in the family of iron−sulfur proteins, which are distinguished not only by their cluster ligation patterns but also by the chemistry used in catalyzing a simple, albeit mechanistically challenging, reaction.

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