tryptophan C-mannosyltransferase (CMT enzyme protein)

see also:

• cytokines

• discovered in 2022¹⁾, tryptophan C-mannosyltransferase (CMT) is a small enzyme protein which results in C-mannosylation of tryptophan side chains or some 20% of all secretory proteins and is important in cell-to-cell communications especially with cytokines and adhesion GPCRs which are important in neuronal growth acting as “sensory antennae” as the growing neuron makes its way through the brain, while the human CMT variant CMT2 plays a key role in sperm development
• CMT is a member of the category C (GT-C) glycosyltransferase enzymes, one of the three glycosyltransferase superfamilies
  • the most prominent member is oligosaccharyltransferase (OST), which is responsible for N-glycosylation
  • similar to the OST, the CMT also recognises highly specific sequences in proteins, with the difference, however, that in mammals four different CMTs occur simultaneously, which also recognise different protein sequences
  • CMT creates a unique carbon-carbon bond between protein and sugar
    • the sugar substrates of the CMT are complex to produce due to their lipid binding and are therefore particularly valuable. CMT initially binds them in a non-reactive protected binding pocket. Only when the protein or peptide to be modified docks onto the CMT is the sugar substrate shifted by a peptide sensor and brought into a highly reactive state.
• in multicellular organisms, there are three types of protein glycosylation. N-glycosylation, O-mannosylation and C-mannosylation.
  • all of these processes take place in the endoplasmic reticulum, and in all of them enzymes attach sugar residues to specific sites in newly forming protein.
• the malaria pathogen Plasmodium falciparum, has its own CMT and needs it to attach to the host