Structural insight into an intertwined homodimer of the N-terminal domain of hypothetical protein Rv1421 from Mycobacterium tuberculosis H37Rv.

Mycobacterium tuberculosis Rv1421 (MtRv1421) is a hypothetical protein that may participate in the nucleotide-sugar metabolism for cell wall homeostasis. Our previous studies have suggested that MtRv1421 may be involved in the regulatory device mediated by uridine diphosphate N-acetylglucosamine (UDP-GlcNAc), a precursor in peptidoglycan synthesis. However, the detailed molecular functions of MtRv1421 are unclear due to a lack of structural information. To elucidate its functional domain structure, we have constructed the truncated MtRv1421 containing the N-terminal domain (MtRv1421-NTD) and determined its crystal structure at a resolution of 1.7 Å. The overall structure of MtRv1421-NTD showed an intertwined homodimer in which the β5 strand and α6 helix of one subunit were exchanged with those of the other. In addition, the crystal structure of MtRv1421-NTD contained an atypical kinase fold caused by an open conformation of the hinge region between the α4 and α5 helices of each subunit. Our results provide structural insights into the molecular understanding of MtRv1421, including interactions between its functional domains and the binding of UDP-GlcNAc to the putative ligand-binding pocket of MtRv1421-NTD.