Riboflavin is also known as Vitamin B2 and is the key component of FAD and FMN. These are known as flavocoenzymes and participate in redox reactions in a wide range of cellular pathways. These include:
- metabolism of fats, proteins and carbohydrates
- electron transport chain
- metabolism of drugs and toxins
- production of other vitamins
- iron metabolism
Good sources of riboflavin include leafy green vegetables, milk, legumes, mushrooms, liver and yeast. The name riboflavin comes from ribose (the reduced form, ribitol, is a part of the structure) and flavin - the ring moiety which gives the oxidised molecule a yellow colour (from the Latin flavus, ‘yellow’).
RibU has a riboflavin-binding pocket that has an approximate width of 15Å and a thickness of 8Å, and is hydrophobic. The pocket is on the periplasmic side of RibU and is formed by 13 conserved amino acids. It was decided that riboflavin placement would be modelled after the placement of all protein atoms had been resolved. Because riboflavin has a ribityl side chain (with four hydroxyl groups) and an aromatic ring (polar on one side and hydrophobic on the other) this suggests there is only one possible orientation of riboflavin in the RibU binding site. Riboflavin is recognised by numerous hydrogen bonds – in particular with Asn 131 and Asn 164 which are invariant in RibU homologues. Riboflavin also forms van der Waals interactions with the binding pocket residues. RibU and Riboflavin have a binding affinity of 0.6nM (Rib U from L. lactis).
Possible mechanism:
The actual purpose of the L1 loop is uncertain; however it is thought to be involved in recognition of riboflavin in conjunction with trans-membrane segments 4-6. Once the riboflavin has bound the L1 loop is thought to act as a gate, where the L1 loop may close to allow interaction with riboflavin. This in turn allows the A, A’ and T components to force the first portion of RibU (TM segments 1-3) apart from the second portion of RibU (TM segments 4-6) with the aid of ATP hydrolysis. RibU then adopts a transient, inward open conformation. These changes may all contribute to a disruption of the RibU interactions with riboflavin, allowing the release of riboflavin into the cytoplasm. The ADP that remains bound to RibU may also cause the resetting of the RibU structure to its closed state.
