Identification of M. tuberculosis IspE and purification strategy. Panel a: Alignment of the amino acid sequence of E. coli IspE (ECO) and the putative IspE amino acids of M. tuberculosis (Rv1011) (MTB), B. mallei (BMA), S. Typhi (STY), V. cholerae (VCH), and previously characterized Aquifex aeolicus (AAE) (Sgraja et al., 2008). Identities are highlighted in black and similarities in gray. The amino acids reported to be involved in CDP-ME binding (I) and ATP-binding (II + III) reported in E. coli IspE (Miallau et al., 2003) are underlined. Panel b: Rv1011 contains two predicted kinase motifs, a homoserine (ThrB) kinase (a.a. 36-299) and a GHMP Kinase (a.a. 88-268)]. A series of eight fragments were engineered as indicated. Panel c: Characteristics of the eight recombinant Rv1011 fragments. The primers used to amplify the fragments are listed in Supplemental Data S3. The solubility was determined by using SDS-PAGE analysis and the activities were determined using the radioisotope based in vitro IspE assay. − no; +, low; ++, intermediate; +++, good.