Analysis of the crystal structures of the tetrameric Mlc/EIIB complex shows a molecular mechanism of Mlc inactivation by membrane sequestration, in which Mlc loses its DNA binding ability in vivo due to the conformational obstruction by EIIB molecules [17] Mlc is able to bind to the dephosphorylated EIIB domain of NagE when the NagE level is high [18] The crystal structure of Mlc has been determined [19, 20]to 2.85 and 2.7 Å resolution and Mlc in complex with four molecules of enzyme IIBGlc (EIIB) [17] to 2.85 Å resolution. Mlc forms stable dimers and binds to palindromic operator sites. The N-terminal region has a helix-turn-helix domain, and a C-terminal helix is implicated in EIICB^Glc binding [16]. Mlc forms tetramers in solution [2, 16, 19] The Mlc monomer is composed of three domains: a DNA-binding motif (D-domain), an EIICB^Glc-binding motif (E-domain), and an oligomerization domain (O-domain) [17]. Mlc is autoregulated [3, 7] but it is also repressed and activated by CRP [7] Mlc binds to sites with a length of 23 bp. Its consensus sequence has been determined [5] Mlc and VC2007, an ortholog of Mlc in Vibrio cholerae, bind to the same two operator sites in the ptsG upstream regulatory region. In addition, Mlc is capable of binding the upstream region of the ptsG gene from Vibrio cholerae [18] The intracellular concentration of Mlc is very limited [2] Zinc mediates the Mlc repressor function [20] Mlc has a high homology with the NagC transcriptional dual regulator (40% identity and 80% similarity) [12, 21] At the post-transcriptional level, Mlc interacts with MtfA, which is involved in the regulation of the ptsG [22] Mlc is a member of the ROK (repressor, ORFs, kinases) (NagC/XylR) family of proteins, which contains at least two distinct classes of proteins: xylose repressor (XylR) and a series of glucose/fructose kinases [23, 24].