1,3-beta-glucan synthase
Encyclopedia
1,3-beta-glucan synthase is a glucosyltransferase enzyme
involved in the generation of beta-glucan
in fungi. It serves as a pharmacological target for antifungal drug
s such as caspofungin
, anidulafungin
and micafungin.
The biosynthesis
of disaccharides, oligosaccharide
s and polysaccharide
s involves the action of hundreds of different glycosyltransferase
s. These enzyme
s catalyse the transfer of sugar
moieties from activated donor molecule
s to specific acceptor molecules, forming glycosidic bond
s. A classification of glycosyltransferases using nucleotide
diphospho-sugar, nucleotide monophospho-sugar and sugar phosphate
s and related protein
s into distinct sequence
based families has been described. This classification is available on the CAZy (CArbohydrate-Active EnZymes) web site . The same three-dimensional fold
is expected to occur within each of the families. Because 3-D structure
s are better conserved
than sequences, several of the families defined on the basis of sequence
similarities may have similar 3-D structure
s and therefore form 'clans'.
This is the glycosyltransferase 48 family, which consists of various 1,3-beta-glucan synthase
components including Gls1, Gls2 and Gls3 from yeast
. 1,3-beta-glucan synthase
also known as callose synthase catalyses
the formation of a beta-1,3-glucan polymer
that is a major component of the fungal
cell wall
. The reaction catalysed is:-
UDP-glucose + {(1,3)-beta-D-glucosyl}(N) = UDP + {(1,3)-beta-D-glucosyl}(N+1).
Enzyme
Enzymes are proteins that catalyze chemical reactions. In enzymatic reactions, the molecules at the beginning of the process, called substrates, are converted into different molecules, called products. Almost all chemical reactions in a biological cell need enzymes in order to occur at rates...
involved in the generation of beta-glucan
Beta-glucan
β-Glucans are polysaccharides of D-glucose monomers linked by β-glycosidic bonds. β-glucans are a diverse group of molecules that can vary with respect to molecular mass, solubility, viscosity, and three-dimensional configuration...
in fungi. It serves as a pharmacological target for antifungal drug
Antifungal drug
An antifungal medication is a medication used to treat fungal infections such as athlete's foot, ringworm, candidiasis , serious systemic infections such as cryptococcal meningitis, and others...
s such as caspofungin
Caspofungin
Caspofungin is an antifungal drug, the first of a new class termed the echinocandins from Merck & Co., Inc. It shows activity against infections with Aspergillus and Candida, and works by inhibiting the enzyme β-D-Glucan synthase and thereby disturbing the integrity of the fungal cell wall...
, anidulafungin
Anidulafungin
Anidulafungin or Eraxis is an antifungal drug originally manufactured and submitted for FDA approval by Vicuron Pharmaceuticals. Pfizer acquired the drug upon its acquisition of Vicuron in the fall of 2005. Pfizer gained approval by the Food and Drug Administration on February 21, 2006; it was...
and micafungin.
The biosynthesis
Biosynthesis
Biosynthesis 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...
of disaccharides, oligosaccharide
Oligosaccharide
An oligosaccharide is a saccharide polymer containing a small number of component sugars, also known as simple sugars...
s and polysaccharide
Polysaccharide
Polysaccharides are long carbohydrate molecules, of repeated monomer units joined together by glycosidic bonds. They range in structure from linear to highly branched. Polysaccharides are often quite heterogeneous, containing slight modifications of the repeating unit. Depending on the structure,...
s involves the action of hundreds of different glycosyltransferase
Glycosyltransferase
Glycosyltransferases are enzymes that act as a catalyst for the transfer of a monosaccharide unit from an activated nucleotide sugar to a glycosyl acceptor molecule, usually an alcohol....
s. These enzyme
Enzyme
Enzymes are proteins that catalyze chemical reactions. In enzymatic reactions, the molecules at the beginning of the process, called substrates, are converted into different molecules, called products. Almost all chemical reactions in a biological cell need enzymes in order to occur at rates...
s catalyse the transfer of sugar
Sugar
Sugar is a class of edible crystalline carbohydrates, mainly sucrose, lactose, and fructose, characterized by a sweet flavor.Sucrose in its refined form primarily comes from sugar cane and sugar beet...
moieties from activated donor molecule
Molecule
A molecule is an electrically neutral group of at least two atoms held together by covalent chemical bonds. Molecules are distinguished from ions by their electrical charge...
s to specific acceptor molecules, forming glycosidic bond
Glycosidic bond
In chemistry, a glycosidic bond is a type of covalent bond that joins a carbohydrate molecule to another group, which may or may not be another carbohydrate....
s. A classification of glycosyltransferases using nucleotide
Nucleotide
Nucleotides are molecules that, when joined together, make up the structural units of RNA and DNA. In addition, nucleotides participate in cellular signaling , and are incorporated into important cofactors of enzymatic reactions...
diphospho-sugar, nucleotide monophospho-sugar and sugar phosphate
Phosphate
A phosphate, an inorganic chemical, is a salt of phosphoric acid. In organic chemistry, a phosphate, or organophosphate, is an ester of phosphoric acid. Organic phosphates are important in biochemistry and biogeochemistry or ecology. Inorganic phosphates are mined to obtain phosphorus for use in...
s and related protein
Protein
Proteins are biochemical compounds consisting of one or more polypeptides typically folded into a globular or fibrous form, facilitating a biological function. A polypeptide is a single linear polymer chain of amino acids bonded together by peptide bonds between the carboxyl and amino groups of...
s into distinct sequence
Sequence (biology)
A sequence in biology is the one-dimensional ordering of monomers, covalently linked within in a biopolymer; it is also referred to as the primary structure of the biological macromolecule.-See also:* Protein sequence* DNA sequence...
based families has been described. This classification is available on the CAZy (CArbohydrate-Active EnZymes) web site . The same three-dimensional fold
Protein folding
Protein folding is the process by which a protein structure assumes its functional shape or conformation. It is the physical process by which a polypeptide folds into its characteristic and functional three-dimensional structure from random coil....
is expected to occur within each of the families. Because 3-D structure
Secondary structure
In biochemistry and structural biology, secondary structure is the general three-dimensional form of local segments of biopolymers such as proteins and nucleic acids...
s are better conserved
Conserved sequence
In biology, conserved sequences are similar or identical sequences that occur within nucleic acid sequences , protein sequences, protein structures or polymeric carbohydrates across species or within different molecules produced by the same organism...
than sequences, several of the families defined on the basis of sequence
Sequence
In mathematics, a sequence is an ordered list of objects . Like a set, it contains members , and the number of terms is called the length of the sequence. Unlike a set, order matters, and exactly the same elements can appear multiple times at different positions in the sequence...
similarities may have similar 3-D structure
Cis-regulatory element
A cis-regulatory element or cis-element is a region of DNA or RNA that regulates the expression of genes located on that same molecule of DNA . This term is constructed from the Latin word cis, which means "on the same side as". These cis-regulatory elements are often binding sites for one or...
s and therefore form 'clans'.
This is the glycosyltransferase 48 family, which consists of various 1,3-beta-glucan synthase
Synthase
In biochemistry, a synthase is an enzyme that catalyses a synthesis process.Following the EC number classification, they belong to the group of ligases, with lyases catalysing the reverse reaction....
components including Gls1, Gls2 and Gls3 from yeast
Saccharomyces cerevisiae
Saccharomyces cerevisiae is a species of yeast. It is perhaps the most useful yeast, having been instrumental to baking and brewing since ancient times. It is believed that it was originally isolated from the skin of grapes...
. 1,3-beta-glucan synthase
Thromboxane-A synthase
Thromboxane A synthase 1 , also known as TBXAS1, is an enzyme that, in humans, is encoded by the TBXAS1 gene.- Function :This gene encodes a member of the cytochrome P450 superfamily of enzymes...
also known as callose synthase catalyses
Catalysis
Catalysis is the change in rate of a chemical reaction due to the participation of a substance called a catalyst. Unlike other reagents that participate in the chemical reaction, a catalyst is not consumed by the reaction itself. A catalyst may participate in multiple chemical transformations....
the formation of a beta-1,3-glucan polymer
Polymer
A polymer is a large molecule composed of repeating structural units. These subunits are typically connected by covalent chemical bonds...
that is a major component of the fungal
Fungus
A fungus is a member of a large group of eukaryotic organisms that includes microorganisms such as yeasts and molds , as well as the more familiar mushrooms. These organisms are classified as a kingdom, Fungi, which is separate from plants, animals, and bacteria...
cell wall
Cell wall
The cell wall is the tough, usually flexible but sometimes fairly rigid layer that surrounds some types of cells. It is located outside the cell membrane and provides these cells with structural support and protection, and also acts as a filtering mechanism. A major function of the cell wall is to...
. The reaction catalysed is:-
UDP-glucose + {(1,3)-beta-D-glucosyl}(N) = UDP + {(1,3)-beta-D-glucosyl}(N+1).