enzymology Enzymes () are proteins that act as biological catalysts by accelerating chemical reactions. The molecules upon which enzymes may act are called substrates, and the enzyme converts the substrates into different molecules known as products. A ...

, a dTDP-4-dehydrorhamnose 3,5-epimerase () is an enzyme that

catalyzes Catalysis () is the process of increasing the rate of a chemical reaction by adding a substance known as a catalyst (). Catalysts are not consumed in the reaction and remain unchanged after it. If the reaction is rapid and the catalyst recyc ...

the chemical reaction :dTDP-4-dehydro-6-deoxy-D-glucose

\rightleftharpoons

dTDP-4-dehydro-6-deoxy-L-mannose Hence, this enzyme has one

substrate Substrate may refer to: Physical layers *Substrate (biology), the natural environment in which an organism lives, or the surface or medium on which an organism grows or is attached ** Substrate (locomotion), the surface over which an organism lo ...

, dTDP-4-dehydro-6-deoxy-D-glucose, and one product, dTDP-4-dehydro-6-deoxy-L-mannose. This enzyme belongs to the family of isomerases, specifically those

racemase Epimerases and racemases are isomerase enzymes that catalyze the inversion of stereochemistry in biological molecules. Racemases catalyze the stereochemical inversion around the asymmetric carbon atom in a substrate having only one center of asym ...

s and epimerases acting on carbohydrates and derivatives. The systematic name of this enzyme class is dTDP-4-dehydro-6-deoxy-D-glucose 3,5-epimerase. Other names in common use include dTDP-L-rhamnose synthetase, dTDP-L-rhamnose synthetase, thymidine diphospho-4-ketorhamnose 3,5-epimerase, TDP-4-ketorhamnose 3,5-epimerase, dTDP-4-dehydro-6-deoxy-D-glucose 3,5-epimerase, and TDP-4-keto-L-rhamnose-3,5-epimerase. This enzyme participates in 3 metabolic pathways:

nucleotide sugars metabolism In nucleotide sugar metabolism a group of biochemicals known as nucleotide sugars act as donors for sugar residues in the glycosylation reactions that produce polysaccharides. They are substrates for glycosyltransferases. The nucleotide sugars ar ...

streptomycin biosynthesis Streptomycin is an antibiotic medication used to treat a number of bacterial infections, including tuberculosis, ''Mycobacterium avium'' complex, endocarditis, brucellosis, ''Burkholderia'' infection, plague, tularemia, and rat bite fever ...

, and

polyketide sugar unit biosynthesis Polyketides are a class of natural products derived from a precursor molecule consisting of a chain of alternating ketone (or reduced forms of a ketone) and methylene groups: (-CO-CH2-). First studied in the early 20th century, discovery, biosynt ...

Structural studies

The crystal structure of RmlC from ''Methanobacterium thermoautotrophicum'' was determined in the presence and absence of a

analogue. RmlC is a homodimer comprising a central jelly roll motif, which extends in two directions into longer beta-sheets. Binding of dTDP is stabilised by ionic interactions to the phosphate group and by a combination of ionic and hydrophobic interactions with the base. The

active site In biology and biochemistry, the active site is the region of an enzyme where substrate molecules bind and undergo a chemical reaction. The active site consists of amino acid residues that form temporary bonds with the substrate (binding site) a ...

, which is located in the centre of the jelly roll, is formed by residues that are conserved in all known RmlC sequence homologues. The

is lined with a number of charged residues and a number of residues with hydrogen-bonding potentials, which together comprise a potential network for substrate binding and catalysis. The active site is also lined with aromatic residues which provide favourable environments for the base moiety of dTDP and potentially for the

sugar Sugar is the generic name for sweet-tasting, soluble carbohydrates, many of which are used in food. Simple sugars, also called monosaccharides, include glucose, fructose, and galactose. Compound sugars, also called disaccharides or double ...

moiety of the

. As of late 2007, 14 structures have been solved for this class of enzymes, with PDB accession codes , , , , , , , , , , , , , and .

Structural studies

References

Further reading