Crystal structure of the polyketide cyclase from <i>Mycobacterium tuberculosis</i>

About 40% of proteins are classified as conserved hypothetical proteins in Mycobacterium tuberculosis (TB). Identification and characterization of these proteins are beneficial to understand the pathogenesis of TB and exploiting novel drugs for TB treatments. The polyketide cyclase, a protein from M. tuberculosis ( Mt PC) has been annotated as a hypothetical protein in Uniprot database. Sequence analysis shows that the Mt PC belongs to the NTF2-like superfamily proteins with diverse functions. Here, we determined the crystal structure of Mt PC at a resolution of 2.4 Å and measured backbone relaxation parameters for the Mt PC protein. Mt PC exists as a dimer in solution, and each subunit contains a six-stranded mixed β-sheet and three α helixes which are arranged in the order α1-α2-β1-β2-α3-β3-β4-β5-β6. The NMR dynamics analysis showed that the overall structure of Mt PC is highly rigid on ps-ns time scales. Furthermore, we predicted the potential function of Mt PC based on the crystal structure. Our results lay the basis for further exploiting and mechanistically understanding the biological functions of Mt PC.