{Protbox
|Name=Riboflavin Synthase
|Photo=crystal%20structure.jpg
|Caption=
{{Protbox
|Name=Riboflavin Synthase
|Photo=crystal%20structure.jpg
|Caption=
{{Protbox
|Name=Riboflavin Synthase
|Photo=crystal%20structure.jpg
|Caption=
{{Protbox
|Name=Riboflavin Synthase
|Photo=crystal%20structure.jpg
|Caption=
{{Protbox
|Name=Riboflavin Synthase
|Photo=crystal%20structure.jpg
|Caption={{{!}} align="center" border="0"
{{!}}
Enzyme
{{!}} Riboflavin Synthase
{{!}}-
{{!}}
PDB Code
{{!}} {{PDB|1i8d}}
{{!}}-
{{!}}
Organism
{{!}}
Escherichia coliEscherichia coli , is a Gram negative bacterium that is commonly found in the lower intestine of warm-blooded organisms . Most E...
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Riboflavin synthase is an
enzymeEnzymes are proteins that catalyze chemical reactions. In enzymatic reactions, the molecules at the beginning of the process are called substrates, and the enzyme converts them into different molecules, called the products. Almost all processes in a biological cell need enzymes to occur at...
that catalyzes the final reaction of riboflavin
biosynthesisBiosynthesis is an enzyme-catalyzed process in cells of living organisms by which substrates are converted to more complex products. The biosynthesis process often consists of several enzymatic steps in which the product of one step is used as substrate in the following step...
:
(2)
6,7-dimethyl-8-ribityllumazine6,7-Dimethyl-8-ribityllumazine is a precursor for riboflavin. It is acted upon by riboflavin synthase....
→
riboflavinRiboflavin , also known as vitamin B
2, is an easily absorbed micronutrient with a key role in maintaining health in humans and animals. It is the central component of the cofactors FAD and FMN, and is therefore required by all flavoproteins. As such, vitamin B
2 is required...
+ 5-amino-6-ribitylamino-2,4(1
H,3
H)-pyrimidinedione
----
Riboflavin synthase is a
homotrimerthumbnail|right|400px|Trimeric form of a TNF-α mutantA Homotrimer is a protein composed of three identical units of polypeptide....
with 23kDa subunits.
{Protbox
|Name=Riboflavin Synthase
|Photo=crystal%20structure.jpg
|Caption=
{{Protbox
|Name=Riboflavin Synthase
|Photo=crystal%20structure.jpg
|Caption=
{{Protbox
|Name=Riboflavin Synthase
|Photo=crystal%20structure.jpg
|Caption=
{{Protbox
|Name=Riboflavin Synthase
|Photo=crystal%20structure.jpg
|Caption=
{{Protbox
|Name=Riboflavin Synthase
|Photo=crystal%20structure.jpg
|Caption={{{!}} align="center" border="0"
{{!}}
Enzyme
{{!}} Riboflavin Synthase
{{!}}-
{{!}}
PDB Code
{{!}} {{PDB|1i8d}}
{{!}}-
{{!}}
Organism
{{!}}
Escherichia coliEscherichia coli , is a Gram negative bacterium that is commonly found in the lower intestine of warm-blooded organisms . Most E...
{{!}}}
|Gene_type=
|Molecular_weight=
|Structure=
|Type=
|Functions=
|Domains=
|Motifs=
|Alternative_products=
|Catalytic_activity=
|Cofactors=
|Enzyme_regulation=
|Diseases=
|Pharmaceuticals=
|Taxa=
|Cells=
|Location=
|Names=
|Pathways=
|Interactions=
|Pages=
|Review=
}}
Riboflavin synthase is an
enzymeEnzymes are proteins that catalyze chemical reactions. In enzymatic reactions, the molecules at the beginning of the process are called substrates, and the enzyme converts them into different molecules, called the products. Almost all processes in a biological cell need enzymes to occur at...
that catalyzes the final reaction of riboflavin
biosynthesisBiosynthesis is an enzyme-catalyzed process in cells of living organisms by which substrates are converted to more complex products. The biosynthesis process often consists of several enzymatic steps in which the product of one step is used as substrate in the following step...
:
(2)
6,7-dimethyl-8-ribityllumazine6,7-Dimethyl-8-ribityllumazine is a precursor for riboflavin. It is acted upon by riboflavin synthase....
→
riboflavinRiboflavin , also known as vitamin B
2, is an easily absorbed micronutrient with a key role in maintaining health in humans and animals. It is the central component of the cofactors FAD and FMN, and is therefore required by all flavoproteins. As such, vitamin B
2 is required...
+ 5-amino-6-ribitylamino-2,4(1
H,3
H)-pyrimidinedione
----
Structure
Riboflavin synthase is a
homotrimerthumbnail|right|400px|Trimeric form of a TNF-α mutantA Homotrimer is a protein composed of three identical units of polypeptide....
with 23kDa subunits. Each
monomerA monomer is a small molecule that may become chemically bonded to other monomers to form a polymer...
contains two beta-barrels and one α-helix at the C-terminus (residues 186-206.) The monomer folds into pseudo two-fold symmetry, predicted by sequence similarity between the N-terminus barrels (residues 4-86) and the C-terminus barrel (residues 101-184).
----
Active Site
Two 6,7-dimethyl-8-ribityllumazine molecules are hydrogen bound to each monomer as the two
domainsA protein domain is a part of protein sequence and structure that can evolve, function, and exist independently of the rest of the protein chain. Each domain forms a compact three-dimensional structure and often can be independently stable and folded. Many proteins consist of several structural...
are topologically similar. The
active siteThe active site of an enzyme contains the catalytic and binding sites. The structure and chemical properties of the active site allow the recognition and binding of the substrate....
is located in the interface of the substrates between monomer pairs and modeled structures of the active site
dimerA dimer is a chemical or biological entity consisting of two structurally similar subunits called monomers, which are joined by bonds, which can be strong or weak.- Organic chemistry :...
have been created. Only one of the active sites of the
enzymeEnzymes are proteins that catalyze chemical reactions. In enzymatic reactions, the molecules at the beginning of the process are called substrates, and the enzyme converts them into different molecules, called the products. Almost all processes in a biological cell need enzymes to occur at...
catalyze riboflavin formation at a time as the other two sites face outward and are exposed to
solventA solvent is a liquid, solid, or gas that dissolves another solid, liquid, or gaseous solute, resulting in a solution.The most common solvent in everyday life is water. Most other commonly-used solvents are organic chemicals. These are called organic solvents...
. The
amino acidAmino acids are molecules containing an amine group, a carboxylic acid group and one of the twenty R-groups. These molecules are particularly important in biochemistry, where this term refers to alpha-amino acids with the general formula H
2NCHRCOOH, where R is an organic substituent...
residues involved in hydrogen bonding to the
ligandIn chemistry, a ligand is either an atom, ion, or molecule that binds to a central metal-atom to produce a coordination complex. The bonding between the metal and ligand generally involves formal donation of one or more of the ligand's electron pairs. The metal-ligand bonding ranges from covalent...
are pictured, participating residues may include Thr148, Met160, Ile162, Thr165, Val6, Tyr164, Ser146, and Gly96 at the C-terminal domain and Ser41, Thr50, Gly 62, Ala64, Ser64, Val103, Cys48, His102 at the N-terminal domain.
{{Protbox
|Name=Monomer of Riboflavin Synthase
|Photo=monomer_plus_ligands.jpg
|Caption={{{!}} align="center" border="0"
{{!}}
Substrate
{{!}} Carboxyethyllumazine
{{!}}-
{{!}}
PDB Code
{{!}} {{PDB|1kzl}}
{{!}}-
{{!}}
Organism
{{!}}
S. pombe
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Mechanism
No cofactors are needed for catalysis. Additionally, the formation of riboflavin from 6,7-dimethyl-8-ribityllumazine can occur in boiling aqueous solution in the absence riboflavin synthase.
At the interface of the substrate between monomer pairs, the enzyme holds the two 6,7-dimethyl-8-ribityllumazine molecules in position via hydrogen bonding to catalyze the dismutation reaction. Additionally, acid/base catalysis by the amino acid residues has been suggested. Specific residues may include the His102/Thr148 dyad as a base for deprotonation of the C7a
methyl groupIn chemistry, a methyl group is a hydrophobic alkyl functional group named after methane . It has the formula -3 and is often abbreviated -Me...
. Of the dyad, His102 is from the N-barrel and Thr148 is from the C-barrel, highlighting the importance of the proximity of the two subunits of the enzyme in the early stages of the reaction. It has also been suggested that the identity of the
nucleophileIn chemistry, a nucleophile is a reagent that forms a chemical bond to its reaction partner by donating both bonding electrons. Because nucleophiles donate electrons, they are by definition Lewis bases . All molecules or ions with a free pair of electrons can act as nucleophiles...
is one of the following conserved residues: Ser146, Ser41, Cys48, or Thr148, or water in the uncatalyzed reaction. In studies on the role of Cys48 as a possible nucleophile, it has not been determined if nucleophilic displacement occurs via an SN1 or SN2 reaction.
image:mech 1.jpg
image:mech 2.jpg
image:mech 3.jpg
image:mech 4.jpg
Drug Production
Scientists have hypothesized that enzymes involved in the riboflavin biosynthesis pathway, including riboflavin synthase, can be used to develop antibacterial drugs in order to treat infections caused by Gram-negative bacteria and yeasts. This hypothesis is based on the inability of Gram-negative bacteria, such as E. coli and S. typhimurium, to uptake riboflavin from the external environment. As Gram-negative bacteria need to produce their own riboflavin, inhibiting riboflavin synthase or other enzymes involved in the pathway may be useful tools in developing antibacterial drugs.
The most potent riboflavin synthase
inhibitorSomething that restrains, blocks, or suppresses.Inhibitor or inhibition may refer to:* Corrosion inhibitor, a substance that decreases the rate of metal oxidation...
is 9-D-ribityl-1,3,7-trihydropurine-2,6,8-trione, with Ki value of 0.61 μM. 9-D-ribityl-1,3,7-trihydropurine-2,6,8-trione is thought to work through
competitive inhibitionCompetitive inhibition is a form of enzyme inhibition where binding of the inhibitor to the enzyme prevents binding of the substrate and vice versa.-Mechanism:...
with 6,7-dimethyl-8-ribityllumazine.