Gene locus comprising three major allelic glycosyltransferases that generate the A, B, and O blood groups.

An organic compound derived from a hemiacetal by reaction with an alcohol. If the hemiacetal is a sugar, the acetal is a glycoside.

A protein on the surface of bacteria, viruses, or parasites that binds to a ligand present on the surface of a host cell.

A measure of the strength of interaction between a receptor and its ligand.

The clumping of cells in the presence of a protein (e.g., antibody or lectin). The related term hemagglutination denotes the specific case wherein the cells are red blood cells.

Non-carbohydrate portion of a glycoconjugate or glycoside that is glycosidically linked to the glycan through the reducing terminal sugar.

A monosaccharide with an aldehyde group or potential aldehydic carbonyl group (by definition, this is the C-1 position).

A monosaccharide in which an alcoholic hydroxyl group is replaced by an amino group.

The carbon atom of a monosaccharide that bears the hemiacetal functionality (C-1 for most sugars; C-2 for sialic acids).

Stereoisomers of a monosaccharide that differ only in configuration at the anomeric carbon of the ring structure.

A branch of an oligosaccharide emanating from a “core” structure.

See Fondaparinux.

See N-glycan.

A measure of the combined strength of interaction from the multiple affinities of a multivalent complex.

A functional group comprising three nitrogen atoms bound in a linear arrangement (N₃).

A monosaccharide to which an azido group has been introduced synthetically.

See Undecaprenol.

The cleavage of a C-O or C-N bond positioned on the beta carbon with respect to a carbonyl group. The process is used to cleave O-glycans from Ser or Thr residues.

Community of bacteria that adheres to a moist surface (e.g., surface of ponds or teeth).

A class of Ca⁺⁺-dependent lectins recognizable by a characteristic sequence comprising their carbohydrate recognition domain.

Membrane-bound protein chaperone that mediates quality control of protein folding in the endoplasmic reticulum.

Soluble protein chaperone that mediates quality control of protein folding in the endoplasmic reticulum.

An analytical technology using high voltage across the span of a small-diameter capillary to accomplish separation. It is applicable to small quantities of carbohydrates and can interface with a mass spectrometer.

A protective extracellular polysaccharide coat surrounding certain bacteria. Presence of a capsular polysaccharide is often associated with virulence.

A generic term used interchangeably in this book with sugar, saccharide, or glycan. Includes monosaccharides, oligosaccharides, and polysaccharides, as well as derivatives of these compounds.

The domain of a polypeptide that is specifically involved in binding to carbohydrate; in lectins, often a highly evolutionarily conserved region of the polypeptide.

A glycosylated amino acid used in solid-phase peptide synthesis to generate glycopeptides.

Denoting “Carbohydrate Active enZYmes,” this database describes the families of structurally related catalytic and carbohydrate-binding modules (or functional domains) of enzymes that degrade, modify, or create glycosidic bonds.

A repeating homopolymer of β1-4-linked glucose residues.

The common lipid component of glycosphingolipids, composed of a long-chain amino alcohol (sphingosine) and an amide-linked fatty acid.

A glycolipid composed of ceramide with an attached galactose (galactosylceramide) or glucose (glucosylceramide).

A term referring to the position of a resonance in an NMR spectrum.

Glycan synthesis that uses both chemical and enzymatic transformations to obtain the desired product.

A repeating homopolymer of β1-4-linked N-acetylglucosamine residues; the main component of the cell walls of fungi and the exoskeletons of arthropods, among other functions.

A type of glycosaminoglycan defined by the disaccharide unit (GalNAcβ1-4GlcAβ1-3)_n, modified with ester-linked sulfate at certain positions and typically found covalently linked to a proteoglycan core protein.

An inheritable genetic disorder in which mutations have led to improper assembly of glycans, primarily N-glycans.

A vaccine consisting of an antigen (frequently a glycan) coupled to a carrier protein.

An NMR technique producing a two-dimensional map of connections, usually between vicinal protons. Useful in assignment of spectra and identification of carbohydrate residues.

An imaging technique capable of providing near-atomic level resolution for three-dimensional structures of glycan-binding proteins in frozen noncrystalline preparations.

A monosaccharide in which an alcoholic hydroxyl group is replaced by a hydrogen atom.

A modified form of chondroitin sulfate in which a portion of the D-glucuronate residues are epimerized to L-iduronates.

A terminally saturated polyisoprenoid lipid carrier utilized during the assembly of N-glycans and GPI anchors and the O- and C-mannosylation of proteins in the endoplasmic reticulum.

A mass spectrometry fragmentation and ionization technique useful in determining sites of glycosylation on peptides and proteins.

A commonly used method for producing charged species for mass spectrometry analysis.

An enzyme that catalyzes the cleavage of an internal glycosidic linkage in an oligosaccharide or polysaccharide.

See Lipid A.

Small protein motifs (∼40 amino acids) with six conserved cysteine residues that form three disulfide bonds. These often serve as sites for glycan modification.

An enzyme that catalyzes racemization of a chiral center in a sugar.

Two isomeric monosaccharides differing only in the configuration of a single chiral carbon. For example, mannose is the C-2 epimer of glucose.

The part of a molecule that is recognized by a specific antibody or receptor.

A circulating glycosylated cytokine used to treat anemias.

An enzyme that cleaves a monosaccharide from the outer (nonreducing) end of an oligosaccharide, polysaccharide, or glycoconjugate.

Heat-labile, proteinaceous toxins secreted by bacteria that cause illness.

A method for generating semisynthetic proteins by the condensation of a synthetic peptide and a recombinant protein. Glycoproteins can be generated by condensation of a synthetic glycopeptide and a recombinant protein.

A complex array of secreted molecules including glycoproteins, proteoglycans, and/or polysaccharides and structural proteins. In plants, the extracellular matrix is also referred to as the cell wall.

Receptors that recognize glycans from a different organism and consist mostly of pathogenic microbial adhesins, agglutinins, or toxins.

Proteinaceous fiber-like appendages found in many Gram-negative bacteria.

A two-dimensional representation of a three-dimensional organic molecule devised by Hermann Emil Fischer.

A technology that combines glycan derivatization and gel electrophoresis for the analysis of small quantities of carbohydrates.

A synthetic heparin (also called Arixtra) used as an anticoagulant.

Family of proteins that modify Notch activity by catalyzing the transfer of N-acetylglucosamine from UDP-GlcNAc to fucose on an EGF-like repeat.

Five-membered (four carbons and one oxygen, i.e., an oxygen heterocycle) ring form of a monosaccharide named after the structurally similar compound furan.

S-type (sulfhydryl-dependent) β-galactoside-binding lectins, usually occurring in a soluble form, expressed by a wide variety of animal cell types and distinguishable by the amino acid sequence of their carbohydrate recognition domains.

Anionic glycosphingolipid containing one or more residues of sialic acid.

A DNA microarray used to quantify transcript levels in high-throughput format.

The complete genetic sequence of one set of chromosomes.

A generic term for any sugar or assembly of sugars, in free form or attached to another molecule, used interchangeably in this book with saccharide or carbohydrate.

A collection of glycans attached to a surface in a spatially addressed manner.

Proteins that recognize and bind to specific glycans and mediate their biological function. See Lectin and Glycosaminoglycan-binding protein.

The nonenzymatic, chemical modification of proteins by addition of carbohydrate, usually through a Schiff-base reaction with the amino group of the side chain of lysine and subsequent Amadori rearrangement to give a stable conjugate. Not to be confused with (enzymatic) glycosylation.

Study of the structure, chemistry, biosynthesis, and biological functions of glycans and their derivatives.

Altering the biosynthetic machinery for glycoconjugates in a given cell for the production of defined glycoconjugates.

The cell coat consisting of glycans and glycoconjugates surrounding animal cells that is seen as an electron-dense layer by electron microscopy.

A molecule in which one or more glycan units are covalently linked to a noncarbohydrate entity.

Different molecular forms of a glycoprotein, resulting from variable glycan structure and/or glycan attachment site occupancy.

A polysaccharide comprising α1-4 and α1-6-linked glucose residues that functions in short-term energy storage in animals; sometimes referred to as animal starch.

A protein that acts as a primer for glycogen synthesis.

General term denoting a molecule containing a saccharide linked to a lipid aglycone. In higher organisms, most glycolipids are glycosphingolipids, but glycoglycerolipids and other types exist.

The total collection of glycans synthesized by a cell, tissue, or organism under specified conditions of time, space, and environment.

Systematic analysis of the glycome.

Noncarbohydrate compounds that mimic the properties of saccharides.

Carbohydrate component of a glycoconjugate.

A peptide having one or more covalently attached glycan.

A protein with one or more covalently bound glycan.

The systems-level analysis of glycoproteins, including their protein identities, sites of glycosylation, and glycan structures.

Polysaccharide side-chains of proteoglycans or free complex polysaccharides composed of linear disaccharide repeating units, each composed of a hexosamine and a hexose or a hexuronic acid (see Heparin, Heparan sulfate, Chondroitin sulfate, Dermatan sulfate, and Hyaluronan).

Proteins that recognize and bind to specific glycosaminoglycans.

An enzyme that catalyzes the hydrolysis of glycosidic bonds in a glycan. See Exoglycosidase and Endoglycosidase.

A glycan containing at least one glycosidic linkage to another glycan or an aglycone.

Linkage of a monosaccharide to another residue via the anomeric hydroxyl group. The linkage generally results from the reaction of a hemiacetal with an alcohol (e.g., a hydroxyl group on another monosaccharide or amino acid) to form an acetal. Glycosidic linkages between two monosaccharides have defined regiochemistry and stereochemistry.

Glycolipid containing a glycan glycosidically attached to the primary hydroxyl group of ceramide.

The nucleophile in a glycosylation reaction, usually containing a free hydroxyl group.

The electrophile in a glycosylation reaction; the nucleotide sugar in an enzymatic glycosylation reaction.

The enzyme-catalyzed covalent attachment of a carbohydrate to a polypeptide, lipid, polynucleotide, carbohydrate, or other organic compound, generally catalyzed by glycosyltransferases, utilizing specific sugar nucleotide donor substrates.

A membrane anchor that consists of a glycan bridge between phosphatidylinositol and a phosphoethanolamine in amide linkage to the carboxyl terminus of a protein.

Enzyme that catalyzes transfer of a sugar from a sugar nucleotide donor to a substrate.

A small glycan that competes with a more complex ligand for binding to a lectin. More generally, any small molecule that interacts with a receptor or antibody.

A representation of monosaccharides wherein the cyclic structures are depicted as planar rings with the hydroxyl groups orientated above or below the plane of the ring.

The clumping of red blood cells in the presence of a protein (e.g., antibody or lectin).

A lectin that recognizes carbohydrates on the surface of red blood cells and causes hemagglutination.

A compound formed by reaction of an aldehyde with an alcohol group, as in ring closure of an aldose.

A compound formed by reaction of a ketone with an alcohol group, as in ring closure of a ketose.

Glycosaminoglycans defined by the disaccharide unit (GlcNAcα1- 4GlcAβ1-4/IdoAα1-4)_n, containing N- and O-sulfate esters at various positions, and typically found covalently linked to a proteoglycan core protein.

A type of heparan sulfate made by mast cells that has the highest amount of iduronic acid and of N- and O-sulfate residues. Pharmaceutical heparin binds and activates antithrombin.

An NMR technique producing a two-dimensional map correlating chemical shifts of heteronuclei (usually ¹³C for carbohydrates) and chemical shifts of directly bonded protons.

A polysaccharide containing more than one type of monosaccharide.

Hexose with an amino group in place of the hydroxyl group at the C-2 position. Common examples found in vertebrate glycans are the N-acetylated sugars, N-acetylglucosamine and N-acetylgalactosamine.

A 6-carbon monosaccharide typically with an aldehyde (or potential aldehyde) at the C-1 position (aldohexose) and hydroxyl groups at all other positions. Common examples in vertebrate glycans are mannose, glucose, and galactose.

A separation technique frequently used to isolate glycans for analysis or subsequent study.

A polysaccharide composed of only one type of monosaccharide.

A glycosaminoglycan defined by the disaccharide unit (GlcNAcβ1-4GlcAβ1-3)_n that is neither sulfated nor covalently linked to protein; referred to in older literature as hyaluronic acid.

A chemical method that uses hydrazine to cleave amide bonds (e.g., the glycosylamine linkage between a sugar residue and asparagine or the acetamide bond in N-acetylhexosamines).

A class of lectins belonging to the immunoglobulin superfamily.

Receptors that recognize glycans from the same organism. Typically they mediate cell–cell interactions or recognize extracellular molecules, but they can also recognize glycans on the same cell.

Description of tertiary structure common to L-type lectins.

A polylactosamine [Galβ1-4GlcNAcβ1-3]_n with sulfate esters at C-6 of N-acetylglucosamine and galactose residues, found as a side chain of a keratan sulfate proteoglycan.

An organic compound derived from a hemiketal by reaction with an alcohol. If the hemiketal is a sugar, the ketal is a glycoside.

A monosaccharide with a ketone group or a potential ketonic carbonyl group (typically at the C-2 position in natural compounds).

Superfamily of glycan-binding proteins with a common feature of tertiary structure called a “jelly-roll” fold.

The disaccharide Galβ1-4Glc; an abundant milk sugar.

A protein (other than an anticarbohydrate antibody) that specifically recognizes and binds to glycans without catalyzing a modification of the glycan.

A related set of glycans that carry α1-3/1-4 fucose residues covalently linked to galactose or N-acetylglucosamine.

A molecule that is recognized by a specific receptor. In the case of lectins, the ligands are partly or completely glycan-based and are sometimes called counterreceptors.

A protein fold that interacts specifically with hyaluronan.

A technology employing a combination of derivatization of hydroxyl groups, gas chromatography (GC) separation, and mass spectrometry to identify linkage sites in carbohydrate residues.

Lipid that contains fatty acids linked to glucosamine with a variable number of phosphate groups and 1–4 units of ketodeoxyoctulosonic acid (Kdo). See Lipopolysaccharide.

An oligosaccharide linked to dolichol.

Small lateral microdomains of self-associating membrane molecules.

Similar to lipopolysaccharide but lacking the O-antigen polysaccharide side chain repeats.

A bacterial glycolipid composed of a polysaccharide (O-antigen), connected via a core oligosaccharide to lipid A that makes up the major portion of the outer leaflet of the outer membrane of Gram-negative bacteria. A major determinant of antigenic specificity, also known as heat-stable toxin or endotoxin.

Human genetic disorders in which defects in lysosomal enzymes result in the accumulation of various glycans in the lysosomes (e.g., Tay–Sachs disease).

An endo-β-N-acetylhexosaminidase that cleaves the polysaccharide backbone of bacterial peptidoglycan.

Mannose-rich polysaccharide found in certain bacteria, fungi, and plants.

See P-type lectins.

An analysis technique providing masses of ionizable glycans and their fragments in the gas phase. The small sample requirements make it particularly useful.

A procedure commonly used to produce charged species for mass spectrometric analysis.

Highly charged β-glucans that create an osmotic buffer in the periplasmic space of Gram-negative bacteria.

A procedure dependent on metabolic processes in cells to incorporate isotopic or derivatized monosaccharides (or other moieties) into glycans for subsequent analysis.

A method for carbohydrate structure analysis based on the acid stability of methyl ethers and the acid lability of glycosidic linkages; used to determine the linkage positions of monosaccharide residues in an oligosaccharide chain.

The chemical reaction in which a nucleophile attacks the beta carbon of an α,b-unsaturated carbonyl compound. The reaction is used after O-glycan beta elimination in order attach probes to those sites.

A collection of molecules (e.g., DNA, proteins, or glycans) spatially addressed on a surface with micrometer dimensions.

Structural variations in the glycan at any given glycosylation site on a protein (one source of glycoforms).

Strategy some microbial pathogens use to evade immune reactions by decorating themselves with glycans similar to that of their hosts.

A computational technique based on Newton's laws of motion useful in simulating motions and structures of glycans or glycan–protein complexes.

A computational technique useful in predicting binding sites and geometry for glycan–protein complexes.

Carbohydrate that cannot be hydrolyzed into a simpler carbohydrate. The building block of oligosaccharides and polysaccharides. Simple monosaccharides are polyhydroxyaldehydes or polyhydroxyketones with three or more carbon atoms.

Large glycoprotein with a high content of serine, threonine, and proline residues and numerous O-GalNAc-linked saccharides, often occurring in clusters on the polypeptide.

An out-of-date term replaced by the term, glycosaminoglycan. Still used as a group name for human disorders (“mucopolysaccharidoses”) involving glycosaminoglycan accumulation due to genetic deficiency of certain lysosomal enzymes.

The interconversion of stereoisomers at the anomeric center of a monosaccharide.

Having multiple points of interaction. Often seen in oligomeric lectins in which low affinity individual interactions combine to provide high avidity.

A disaccharide with the sequence Galβ1-4GlcNAc.

Glycan covalently linked to the side-chain amide of asparagine residue of a polypeptide chain in the consensus sequence: -Asn-X-Ser/Thr. Unless otherwise stated, the term N-glycan is used generically in this book to denote the most common linkage region, Manβ1-4GlcNAcβ1-4GlcNAcβ1-N-Asn.

(NCL) A technique used to generate large polypeptides by condensation of smaller peptide fragments.

See Sialidase.

Lipooligosaccharide produced by Rhizobium bacteria that stimulates nodule formation and initiates nitrogen fixation in leguminous plants.

Outermost end of an oligosaccharide or polysaccharide chain, opposite to that of the reducing end.

Family of cell-surface receptors that are glycosylated on EGF-like repeats. Ligands include Delta and Serrate/Jagged.

A spectroscopic technique based on detecting precession of magnetically active nuclei in strong magnetic fields. Useful in structure determination of both glycans and protein–glycan complexes as they exist in solution.

An effect on intensities of resonances in NMR spectra that is often related to inter- nuclear distances in the case of proton–proton experiments.

Activated forms of monosaccharides, such as UDP-Gal, GDP-Fuc, and CMP-Sia, typically used as donor substrates by glycosyltransferases.

Membrane-bound proteins that specifically transport nucleotide sugars from the cytosol into the lumen of intracellular organelles (e.g., the Golgi).

See O-glycan.

Dynamic modification of proteins by β-linked N-acetylglucosamine (a posttranslational modification similar to protein phosphorylation).

A glycan glycosidically linked to the hydroxyl group of the amino acids serine, threonine, tyrosine, or hydroxylysine. Unless otherwise stated, the term O-glycan is used in this book to denote the common linkage GalNAcα1-O-Ser/Thr.

Linear or branched chain of monosaccharides attached to one another via glycosidic linkages. The number of monosaccharide units can vary; the term polysaccharide is usually reserved for large glycans with repeating units.

A bacterial polysaccharide consisting of MurNAcβ1-4GlcNAcβ1-4 repeat units, covalently cross-linked to short peptides. Also known as murein, peptidoglycan represents the major structural component of the periplasm.

A reaction using periodate to cleave C–C bonds with vicinal hydroxyl groups (e.g., within carbohydrates) to form the two corresponding aldehydes.

Hair-like appendages on the surface of some bacteria that often contain adhesins.

A lipid polymer composed of repeating units of the unsaturated 5-carbon isoprene unit. See Dolichol and Undecaprenol.

Repeating units of N-acetyllactosamines [Galβ1-4GlcNAcβ1-3]_n, of variable length (sometimes called PolyLacNAc).

The process used to amplify DNA starting from a template DNA strand and complementary oligonucleotide primers.

Glycan composed of repeating monosaccharides, generally greater than ten monosaccharide units in length.

A homopolymer of sialic acids abundant in the brain and fish eggs and found on certain pathogenic bacteria.

A chemical moiety commonly used in glycan synthesis that masks hydroxyl groups in order to prevent them from reacting with other chemical reagents.

A repository containing atomic coordinates primarily for proteins, but also nucleic acids and protein-carbohydrate complexes. Each entry is given a four-element alpha-numeric code.

Any protein with one or more covalently attached glycosaminoglycan chains.

The total collection of proteins in a cell, tissue, or organism, under specific conditions of time, space, and environment.

Class of lectins that recognize mannose-6-phosphate (also called M6P receptors).

A detection procedure based on conduction at high pH and used in HPLC analysis of monosaccharide composition.

Six-membered (five carbons and one oxygen, i.e., an oxygen heterocycle) ring form of a monosaccharide; the most common form found for hexoses and pentoses. The name is based on the structural similarity to the compound “pyran.”

Superfamily of glycan-binding proteins that contain a carbohydrate-recognition domain similar to that in ricin.

A protein that binds to a ligand and initiates signal transmission or other cellular activity. In this book, most receptors are lectins (i.e., they recognize glycans). In microbiology, the terminology is reversed: Adhesins or agglutinins on the microbes bind to receptors which are glycans on the host cell.

End of a glycan that has reducing power because it is unattached to an aglycone and is thus a hemiacetal. In a glycoconjugate, reducing terminus is also used as a synonym for a potential reducing terminus, referring to the end of a glycan covalently attached to the aglycone by a glycosidic bond (i.e., it would have reducing power if it were released).

The region among many possible regions of a molecule that is involved in a chemical reaction. For glycosidic linkages, regiochemistry denotes the hydroxyl group of one monosaccharide that is bound to the anomeric position of the other (i.e., 1-3 vs. 1-4 linkage).

A protein monolayer coating often containing covalently linked glycans and found in the cell envelope of many bacteria and archea.

A generic term for any carbohydrate or assembly of carbohydrates, in free form or attached to another molecule, used interchangeably in this book with carbohydrate and glycan.

A glycoconjugate comprising fatty acyl chains covalently attached directly to a sugar backbone (e.g., Lipid A).

An NMR technique useful in identifying parts of glycans in close approach to protons in the binding sites of protein receptors.

A C-type (Ca⁺⁺-dependent) lectin expressed by cells in the vasculature and bloodstream. The three known selectins are L-selectin/CD62L (expressed by most leukocytes), E-selectin/CD62E (expressed by cytokine-activated endothelial cells), and P-selectin/CD62P (expressed by activated endothelial cells and platelets).

See O-glycan.

Family of acidic sugars with a nine-carbon backbone, of which the most common is N-acetylneuraminic acid, in vertebrates.

Enzyme that releases sialic acid residues from a glycoconjugate. Older name was neuraminidase, now used only refer to the influenza sialidase.

Total array of sialic acid types and linkages expressed by a particular cell tissue or organism, under specified conditions of time, space and environment.

Sialic acid–binding proteins that are members of the I-type lectin family and have an amino-terminal V-set domain with typical conserved residues.

An X-ray scattering technique useful in defining the shape of large molecular complexes as they exist in solution.

Lipids with ceramide as their core structure.

Long-chain amino alcohol (forms ceramide when in amide linkage with a fatty acid).

A generic term often used to refer to any carbohydrate, but most frequently to low-molecular-weight carbohydrates that are sweet in taste. Table sugar, sucrose, is a nonreducing disaccharide (Fruβ2-1αGlc). Oligosaccharides are sometimes called “sugar chains” and individual monosaccharides in a sugar chain are sometimes referred to as “sugar residues.”

An optical technique for the measurement of adsorption of materials onto a surface. Frequently used to estimate affinities of proteins for glycans on coated chips.

A complex polymer consisting of either phosphoglycerol- or phosphoribitol-carrying carbohydrates or amino acids, found on the surface of Gram-positive bacteria.

An analysis technique used in mass spectrometry to separate species of different mass based on velocity differences for particles with equal kinetic energy.

An NMR technique particularly useful in determining the conformation of glycans noncovalently bound to proteins.

Small protein motifs (50–60 amino acids) with six conserved cysteine residues that form three disulfide bonds. Serve as sites for glycan modification.

The total collection of RNA transcripts in a cell, tissue, or organism, under specific conditions of time, space, and environment.

A polyisoprenoid lipid carrier for membrane-bound glycan synthesis in bacteria.

A structure determination technique dependent on scattering of X-rays from molecules ordered in crystals. Useful in the determination of three-dimensional structures of protein–glycan complexes.