FIG 1.

Comparison of cysteine synthases and CysK2 in M. tuberculosis. (A) l-Cysteine production in M. tuberculosis through three pathways. The classical pathway (left), present in most eubacteria and plants, uses CysK1_Mtb for the conversion of O-acetyl-l-serine (OAS) and hydrogen sulfide to l-cysteine. The alternative pathway (right) in M. tuberculosis is based on CysM_Mtb for l-cysteine formation from O-phospho-l-serine (OPS) and thiocarboxylated CysO. The third pathway (middle), based on CysK2, uses OPS and hydrogen sulfide or thiosulfate for cysteine or S-sulfocysteine production, respectively. The organization of the operons including the three cysteine synthases (CysK1, CysM, and CysK2) in the M. tuberculosis H37Rv genome is also shown (http://tbdb.org). (B) Structure-based sequence alignment of CysK1_Mtb, CysM_Mtb, and CysK2 using CysM_Mtb as the reference structure, with the secondary structure elements displayed above the alignments. The position of the invariant lysine residue that covalently binds the cofactor *), residues binding the cofactor phosphate group (●), the motif involved in H-bonding interactions with the substrate carboxylate (black horizontal bar), and the position of the arginine residue responsible for OPS specificity in CysM_Mtb (▲) are indicated. The image in panel B was created with ESPript (35).