The

enzyme 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 ...

dTDP-glucose 4,6-dehydratase ()

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 A chemical reaction is a process that leads to the IUPAC nomenclature for organic transformations, chemical transformation of one set of chemical substances to another. Classically, chemical reactions encompass changes that only involve the pos ...

: dTDP-glucose

\rightleftharpoons

dTDP-4-dehydro-6-deoxy-D-glucose + H₂O

Structure and mechanism of action

The first protein structures of a dTDP-glucose 4,6-dehydratase (RmlB) were completed by Jim Thoden in the Hazel Holden lab (

University of Wisconsin–Madison A university () is an educational institution, institution of higher education, higher (or Tertiary education, tertiary) education and research which awards academic degrees in several Discipline (academia), academic disciplines. Universities ty ...

) and Simon Allard in the Jim Naismith lab (

University of St Andrews (Aien aristeuein) , motto_lang = grc , mottoeng = Ever to ExcelorEver to be the Best , established = , type = Public research university Ancient university , endowment ...

). Further structural, mutagenic, and

enzymatic 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 ...

studies by both groups, along with important mechanistic work by the

W. Wallace Cleland William Wallace Cleland (January 6, 1930 – March 6, 2013, often cited as W. W. Cleland, and known almost universally as "Mo Cleland", was a University of Wisconsin-Madison biochemistry professor. His research was concerned with enzyme reactio ...

and Perry Frey groups have led to a good understanding of this enzyme. In brief summary, the enzyme is a

dimeric protein In biochemistry, a protein dimer is a macromolecular complex formed by two protein monomers, or single proteins, which are usually non-covalently bound. Many macromolecules, such as proteins or nucleic acids, form dimers. The word ''dimer'' has ...

with a Rossmann fold; it uses the tightly bound

coenzyme A cofactor is a non-protein chemical compound or metallic ion that is required for an enzyme's role as a catalyst (a catalyst is a substance that increases the rate of a chemical reaction). Cofactors can be considered "helper molecules" that ass ...

NAD⁺ for transiently oxidizing the substrate, activating it for the

dehydration In physiology, dehydration is a lack of total body water, with an accompanying disruption of metabolic processes. It occurs when free water loss exceeds free water intake, usually due to exercise, disease, or high environmental temperature. Mil ...

step.

Nomenclature

This enzyme belongs to the family of

lyase In biochemistry, a lyase is an enzyme that catalyzes the breaking (an elimination reaction) of various chemical bonds by means other than hydrolysis (a substitution reaction) and oxidation, often forming a new double bond or a new ring structure. ...

s, specifically the hydro-lyases, which cleave carbon-oxygen bonds. The systematic name of this enzyme class is dTDP-glucose 4,6-hydro-lyase (dTDP-4-dehydro-6-deoxy-D-glucose-forming). Other names in common use include thymidine diphosphoglucose oxidoreductase, TDP-glucose oxidoreductase, RmlB, DESIV, and dTDP-glucose 4,6-hydro-lyase. This enzyme participates in 4 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 ...

, streptomycin biosynthesis, polyketide sugar unit biosynthesis, and biosynthesis of vancomycin group antibiotics.

Structure and mechanism of action

Nomenclature

References

Further reading