4.A.1.1.1
Glucose porter (PtsG; GlcA; Umg) (transports D-glucose and α-methyl-D-glucopyranoside).  The IIC domain has been crystallized, and x-ray data to 4.5 Å resolution have been described (Zurbriggen et al. 2010).  A higher resolution structure appeared later (Ren et al. 2018).  The system has been manipulated to engineer increased production of aromatic metabolites (Carmona et al. 2015, Vargas-Tah et al. 2015). The presence or absence of D-glucose reflects the transporter before and after release of the transported glucose into the cytoplasm. The transition associated with substrate release appears to require a subtle structural rearrangement in the region that includes hairpin 1 (Kalbermatter et al. 2017).  Mlc (for makes large colonies) represses transcription of the genes encoding enzyme I, HPr, EIIBC^Glc and EIIABCD^Man in defined media that lack PTS substrates. When glucose is present, the unphosphorylated form of EIIBC^Glc sequesters Mlc to the cell membrane, preventing its interaction with DNA (Plumbridge 2002, Joyet et al. 2013). The Vibrio Mlc functions similarly (Pickering et al. 2014). A small (43 aa) protein, SgrT, acts in tandem with a well-characterized small RNA during metabolic stress, due to the accumulation of cytoplasmic sugar-Ps to help bacterial cells maintain balanced metabolism and continue growing. SgrT acts on the glucose transport system, inhibiting its activity under stress conditions in order to allow cells to utilize alternative carbon sources (Lloyd et al. 2017). ptsG mRNA localization to the inner membrane, coupled with the membrane insertion of nascent peptide, mediates Hfq/SgrS-dependent ptsG mRNA destabilization, presumably by reducing second rounds of translation (Kawamoto et al. 2005). SgrT is a small protein of 43 aas that allosterically inhibits IICB^Glc. while SgrS is a small RNA coompementary to ptsG mRNA that influences its expression.  The sgrST operon is regulated by SgrR, a glucose-6-P-dependent transcriptional activator (Jeckelmann and Erni 2020).  Transport is mediated by an elevator-type mechanism within the IIC^Glc domain, where the substrate binds to the mobile TD (Roth and Fotiadis 2025). This domain undergoes a large-scale rigid-body movement relative to the static scaffold domain, translocating glucose across the membrane. Structures of elevator-type transporters are typically captured in either inward- or outward-facing conformations while intermediate states remain elusive, awaiting structural determination and mechanistic interpretation. Roth and Fotiadis 2025 presented a single-particle cryo-EM structure of purified, n-dodecyl-β-D-maltopyranoside-solubilized IICB^Glc from Escherichia coli. While the IIB^Glc protein domain is flexible, remaining unresolved, the dimeric IIC^Glc transporter is found trapped in a hitherto unobserved intermediate conformational state. Specifically, the TD is located halfway between inward- and outward-facing states. Structural analysis revealed a specific n-dodecyl-β-D-maltopyranoside molecule bound to the glucose binding site. The sliding of the TD is potentially impeded halfway due to the bulky nature of the ligand and a shift of the thin gate, thereby stalling the transporter (Roth and Fotiadis 2025). Biosynthesis of D-allitol from sucrose via engineered modular metabolic pathways has been achieved (Wang et al. 2025).