Structural homology search of the GNE kinase domain using the FATCAT (Flexible structure AlignmenT by Chaining Aligned fragment pairs allowing Twists) server [21] revealed the top four non-redundant hits to be PDB codes 2aa4, 1xc3, 1z05 and 1z6r. All these structures contain the signature zinc-binding motif of the ROK family. The structure of E. coli putative ManNAc kinase (PDB 2aa4) was the top hit with twist-adjusted r.m.s. deviation (opt-rmsd value) of 1.94 Å . The structure of a putative sugar kinase from Bacillus subtilis was the second best hit (PDB 1xc3). The other two homologous structures were transcription repressors that belong to the ROK family (PDB: 1z05 and 1z6r). Vibrio cholerae transcriptional regulator (PDB: 1z05) is a homolog of the E. coli Mlc protein (PDB: 1z6r). The latter is a transcriptional repressor that controls the expression of malT, the central transcription activator of the E. coli maltose system [22] . The structure of the GNE kinase domain aligns well with the E. coli Mlc structure: the N-lobe of GNE kinase domain aligns to the E-domain of Mlc and the C-lobe aligns to the Odomain of Mlc. It is interesting to note that the Mlc O-domain is responsible for the oligomerization of Mlc protein [22] in a way similar to the dimerization of GNE kinase through the C-lobe. However, these four structures do not contain sugar ligands that would help inform on a substrate binding mode for GNE.