Purification, crystallization, and X‐ray diffraction analysis of succinyl‐diaminopimelate desuccinylase from Wolbachia endosymbiont of Brugia malayi

Abstract

Lymphatic filariasis (LF) is a debilitating mosquito‐borne parasitic disease caused by Brugia malayi in humans in the lymphatic system. Although limited drugs are available to treat this disease, these drugs are only effective against the larvae of Brugia malayi. As resistance has been reported to the available drugs, a new antifilarial drug is needed with better prognostic features, a short period of time of use, and efficiency at preventing adult worm survival. In this study, we have targeted succinyl‐diaminopimelate desuccinylase (DapE) from the Wolbachia endosymbiont of Brugia malayi (WBm), which is involved in the production of lysine and meso‐diaminopimelic acid, an essential component for the formation of bacterial cell walls, and plays a vital role in pathogen survival. Deletion of DapE gene is lethal to WBm since the organism has no alternative pathway for lysine biosynthesis. Here, the expression, purification, and crystallization of DapE are reported. The crystals of DapE, with an estimated solvent content of 50.76%, diffract synchrotron X‐rays to a resolution of 2.3 Å and belong to the space group C2221, with unit‐cell parameters of a = 51.78, b = 78.83, and c = 216.20 Å. The X‐ray absorption spectroscopy further confirms that zinc atoms are incorporated in DapE.