Peptidoglycan
Overview
 
Peptidoglycan, also known as murein, is a polymer
Polymer
A polymer is a large molecule composed of repeating structural units. These subunits are typically connected by covalent chemical bonds...

 consisting of sugars and amino acid
Amino acid
Amino acids are molecules containing an amine group, a carboxylic acid group and a side-chain that varies between different amino acids. The key elements of an amino acid are carbon, hydrogen, oxygen, and nitrogen...

s that forms a mesh-like layer outside the plasma membrane of bacteria
Bacteria
Bacteria are a large domain of prokaryotic microorganisms. Typically a few micrometres in length, bacteria have a wide range of shapes, ranging from spheres to rods and spirals...

 (but not Archaea
Archaea
The Archaea are a group of single-celled microorganisms. A single individual or species from this domain is called an archaeon...

), forming the 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 sugar component consists of alternating residues of β-(1,4) linked N-acetylglucosamine
N-Acetylglucosamine
N-Acetylglucosamine is a monosaccharide derivative of glucose. It is an amide between glucosamine and acetic acid...

 and N-acetylmuramic acid
N-Acetylmuramic acid
N-Acetylmuramic acid, or MurNAc, is the ether of lactic acid and N-acetylglucosamine with a chemical formula of C11H19NO8. It is part of a biopolymer in the bacterial cell wall, built from alternating units of N-acetylglucosamine and N-acetylmuramic acid , cross-linked with oligopeptides at the...

. Attached to the N-acetylmuramic acid is a peptide chain of three to five amino acids. The peptide chain can be cross-linked to the peptide chain of another strand forming the 3D mesh-like layer.
Encyclopedia
Peptidoglycan, also known as murein, is a polymer
Polymer
A polymer is a large molecule composed of repeating structural units. These subunits are typically connected by covalent chemical bonds...

 consisting of sugars and amino acid
Amino acid
Amino acids are molecules containing an amine group, a carboxylic acid group and a side-chain that varies between different amino acids. The key elements of an amino acid are carbon, hydrogen, oxygen, and nitrogen...

s that forms a mesh-like layer outside the plasma membrane of bacteria
Bacteria
Bacteria are a large domain of prokaryotic microorganisms. Typically a few micrometres in length, bacteria have a wide range of shapes, ranging from spheres to rods and spirals...

 (but not Archaea
Archaea
The Archaea are a group of single-celled microorganisms. A single individual or species from this domain is called an archaeon...

), forming the 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 sugar component consists of alternating residues of β-(1,4) linked N-acetylglucosamine
N-Acetylglucosamine
N-Acetylglucosamine is a monosaccharide derivative of glucose. It is an amide between glucosamine and acetic acid...

 and N-acetylmuramic acid
N-Acetylmuramic acid
N-Acetylmuramic acid, or MurNAc, is the ether of lactic acid and N-acetylglucosamine with a chemical formula of C11H19NO8. It is part of a biopolymer in the bacterial cell wall, built from alternating units of N-acetylglucosamine and N-acetylmuramic acid , cross-linked with oligopeptides at the...

. Attached to the N-acetylmuramic acid is a peptide chain of three to five amino acids. The peptide chain can be cross-linked to the peptide chain of another strand forming the 3D mesh-like layer. Some Archaea
Archaea
The Archaea are a group of single-celled microorganisms. A single individual or species from this domain is called an archaeon...

 have a similar layer of pseudopeptidoglycan
Pseudopeptidoglycan
Pseudopeptidoglycan is a major cell wall component of some archaea that differs from bacterial peptidoglycan in chemical structure, but resembles eubacterial peptidoglycan in morphology, function, and physical structure...

 or pseudomurein, where the sugar residues are β-(1,3) linked N-acetylglucosamine and N-acetyltalosaminuronic acid
N-Acetyltalosaminuronic acid
N-Acetyltalosaminuronic acid is a uronic acid. It is a component of pseudopeptidoglycan, a structural polymer found in the cell walls in some types of Archaea....

. That is why the cell wall of Archaea is insensitive to lysozyme
Lysozyme
Lysozyme, also known as muramidase or N-acetylmuramide glycanhydrolase, are glycoside hydrolases, enzymes that damage bacterial cell walls by catalyzing hydrolysis of 1,4-beta-linkages between N-acetylmuramic acid and N-acetyl-D-glucosamine residues in a peptidoglycan and between...

. Peptidoglycan serves a structural role in the bacterial cell wall, giving structural strength, as well as counteracting the osmotic pressure of the cytoplasm
Cytoplasm
The cytoplasm is a small gel-like substance residing between the cell membrane holding all the cell's internal sub-structures , except for the nucleus. All the contents of the cells of prokaryote organisms are contained within the cytoplasm...

. A common misconception is that peptidoglycan gives the cell its shape; however, whereas peptidoglycan helps maintain the structural strength of the cell, it is actually the MreB
MreB
MreB is a protein found in bacteria that has been identified as a homologue of actin, as indicated by similarities in tertiary structure and conservation of active site peptide sequence. The conservation of protein structure suggests the common ancestry of the cytoskeletal elements formed by actin,...

 protein that facilitates cell shape . Peptidoglycan is also involved in binary fission during bacterial cell reproduction.

The peptidoglycan layer is substantially thicker in Gram-positive
Gram-positive
Gram-positive bacteria are those that are stained dark blue or violet by Gram staining. This is in contrast to Gram-negative bacteria, which cannot retain the crystal violet stain, instead taking up the counterstain and appearing red or pink...

 bacteria
Bacteria
Bacteria are a large domain of prokaryotic microorganisms. Typically a few micrometres in length, bacteria have a wide range of shapes, ranging from spheres to rods and spirals...

 (20 to 80 nanometers) than in Gram-negative
Gram-negative
Gram-negative bacteria are bacteria that do not retain crystal violet dye in the Gram staining protocol. In a Gram stain test, a counterstain is added after the crystal violet, coloring all Gram-negative bacteria with a red or pink color...

 bacteria (7 to 8 nanometers), with the attachment of the S-layer
S-layer
An S-layer is a part of the cell envelope commonly found in bacteria, as well as among archaea.It consists of a monomolecular layer composed of identical proteins or glycoproteins. This two-dimensional structure is built via self-assembly and encloses the whole cell surface. Thus, the S-layer...

. Peptidoglycan forms around 90% of the dry weight
Dry weight
Dry weight is the weight of a vehicle without any consumables, passengers, or cargo.It is one of the two common weight measurements included in road vehicle specifications, the other one being curb weight....

 of Gram-positive bacteria but only 10% of Gram-negative strains. Thus, presence of high levels of peptidoglycan is the primary determinant of the characterisation of bacteria as gram-positive. In Gram-positive strains, it is important in attachment roles and stereotyping purposes. For both Gram-positive and Gram-negative bacteria, particles of approximately 2 nm can pass through the peptidoglycan.

Structure

The peptidoglycan layer in the bacterial cell wall is a crystal lattice structure formed from linear chains of two alternating amino 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...

s, namely N-acetylglucosamine
N-Acetylglucosamine
N-Acetylglucosamine is a monosaccharide derivative of glucose. It is an amide between glucosamine and acetic acid...

 (GlcNAc or NAG) and N-acetylmuramic acid
N-Acetylmuramic acid
N-Acetylmuramic acid, or MurNAc, is the ether of lactic acid and N-acetylglucosamine with a chemical formula of C11H19NO8. It is part of a biopolymer in the bacterial cell wall, built from alternating units of N-acetylglucosamine and N-acetylmuramic acid , cross-linked with oligopeptides at the...

 (MurNAc or NAM). The alternating sugars are connected by a β-(1,4)-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....

. Each MurNAc is attached to a short (4- to 5-residue) amino acid
Amino acid
Amino acids are molecules containing an amine group, a carboxylic acid group and a side-chain that varies between different amino acids. The key elements of an amino acid are carbon, hydrogen, oxygen, and nitrogen...

 chain, containing D-alanine
Alanine
Alanine is an α-amino acid with the chemical formula CH3CHCOOH. The L-isomer is one of the 20 amino acids encoded by the genetic code. Its codons are GCU, GCC, GCA, and GCG. It is classified as a nonpolar amino acid...

, D-glutamic acid
Glutamic acid
Glutamic acid is one of the 20 proteinogenic amino acids, and its codons are GAA and GAG. It is a non-essential amino acid. The carboxylate anions and salts of glutamic acid are known as glutamates...

, and meso-diaminopimelic acid in the case of Escherichia coli
Escherichia coli
Escherichia coli is a Gram-negative, rod-shaped bacterium that is commonly found in the lower intestine of warm-blooded organisms . Most E. coli strains are harmless, but some serotypes can cause serious food poisoning in humans, and are occasionally responsible for product recalls...

(a Gram negative bacteria) or L-alanine
Alanine
Alanine is an α-amino acid with the chemical formula CH3CHCOOH. The L-isomer is one of the 20 amino acids encoded by the genetic code. Its codons are GCU, GCC, GCA, and GCG. It is classified as a nonpolar amino acid...

, D-glutamine
Glutamine
Glutamine is one of the 20 amino acids encoded by the standard genetic code. It is not recognized as an essential amino acid but may become conditionally essential in certain situations, including intensive athletic training or certain gastrointestinal disorders...

, L-lysine
Lysine
Lysine is an α-amino acid with the chemical formula HO2CCH4NH2. It is an essential amino acid, which means that the human body cannot synthesize it. Its codons are AAA and AAG....

, and D-alanine in the case of Staphylococcus aureus
Staphylococcus aureus
Staphylococcus aureus is a facultative anaerobic Gram-positive coccal bacterium. It is frequently found as part of the normal skin flora on the skin and nasal passages. It is estimated that 20% of the human population are long-term carriers of S. aureus. S. aureus is the most common species of...

(a Gram positive bacteria). These amino acids, except the L-amino acids, do not occur in proteins and are thought to help protect against attacks by most peptidases.

Cross-link
Cross-link
Cross-links are bonds that link one polymer chain to another. They can be covalent bonds or ionic bonds. "Polymer chains" can refer to synthetic polymers or natural polymers . When the term "cross-linking" is used in the synthetic polymer science field, it usually refers to the use of...

ing between amino acid
Amino acid
Amino acids are molecules containing an amine group, a carboxylic acid group and a side-chain that varies between different amino acids. The key elements of an amino acid are carbon, hydrogen, oxygen, and nitrogen...

s in different linear amino sugar chains occurs with the help of the enzyme transpeptidase
Transpeptidase
A transpeptidase is a bacterial enzyme that cross-links the peptidoglycan chains to form rigid cell walls. This enzyme is also known by several other names including DD-peptidase, DD-transpeptidase, D-alanyl-D-alanine carboxypeptidase and serine-type D-Ala-D-Ala carboxypeptidase...

 and results in a 3-dimensional structure that is strong and rigid. The specific amino acid sequence and molecular structure vary with the bacterial species
Species
In biology, a species is one of the basic units of biological classification and a taxonomic rank. A species is often defined as a group of organisms capable of interbreeding and producing fertile offspring. While in many cases this definition is adequate, more precise or differing measures are...

.

Antibiotic inhibition

Some antibacterial drugs such as penicillin
Penicillin
Penicillin is a group of antibiotics derived from Penicillium fungi. They include penicillin G, procaine penicillin, benzathine penicillin, and penicillin V....

 interfere with the production of peptidoglycan by binding to bacterial enzymes known as penicillin-binding proteins or transpeptidase
Transpeptidase
A transpeptidase is a bacterial enzyme that cross-links the peptidoglycan chains to form rigid cell walls. This enzyme is also known by several other names including DD-peptidase, DD-transpeptidase, D-alanyl-D-alanine carboxypeptidase and serine-type D-Ala-D-Ala carboxypeptidase...

s. Penicillin-binding proteins form the bonds between oligopeptide crosslinks in peptidoglycan. For a bacterial cell to reproduce through binary fission, more than a million peptidoglycan subunits (NAM-NAG+oligopeptide) must be attached to existing subunits. Mutations in transpeptidases that lead to reduced interactions with an antibiotic are a significant source of emerging antibiotic resistance
Antibiotic resistance
Antibiotic resistance is a type of drug resistance where a microorganism is able to survive exposure to an antibiotic. While a spontaneous or induced genetic mutation in bacteria may confer resistance to antimicrobial drugs, genes that confer resistance can be transferred between bacteria in a...

.

Considered the human body's own antibiotic
Antibiotic
An antibacterial is a compound or substance that kills or slows down the growth of bacteria.The term is often used synonymously with the term antibiotic; today, however, with increased knowledge of the causative agents of various infectious diseases, antibiotic has come to denote a broader range of...

, lysozyme
Lysozyme
Lysozyme, also known as muramidase or N-acetylmuramide glycanhydrolase, are glycoside hydrolases, enzymes that damage bacterial cell walls by catalyzing hydrolysis of 1,4-beta-linkages between N-acetylmuramic acid and N-acetyl-D-glucosamine residues in a peptidoglycan and between...

s found in tears work by breaking the β-(1,4)-glycosidic bonds in peptidoglycan (see below) and thereby destroying many bacterial cells. Antibiotics such as penicillin commonly target bacterial cell wall formation (of which peptidoglycan is an important component) because animal cells do not have cell walls.

Biosynthesis

The peptidoglycan monomers are synthesized in the cytosol
Cytosol
The cytosol or intracellular fluid is the liquid found inside cells, that is separated into compartments by membranes. For example, the mitochondrial matrix separates the mitochondrion into compartments....

 and are then attached to a membrane carrier bactoprenol
Bactoprenol
Bactoprenol is a lipid synthesized by lactobacilli.Bactoprenol phosphate transports NAM and NAG across the cell membrane in the synthesis of peptidoglycan. Bacitracin inhibits this process....

. Bactoprenol transports peptidoglycan monomers across the cell membrane where they are inserted into the existing peptidoglycan.

In the first step of peptidoglycan synthesis, the glutamine
Glutamine
Glutamine is one of the 20 amino acids encoded by the standard genetic code. It is not recognized as an essential amino acid but may become conditionally essential in certain situations, including intensive athletic training or certain gastrointestinal disorders...

, which is an amino acid, donates an amino group to a sugar, fructose 6-phosphate
Fructose 6-phosphate
Fructose 6-phosphate is fructose sugar phosphorylated on carbon 6 . The β-D-form of this compound is very common in cells. The vast majority of glucose and fructose entering a cell will become converted to this at some point...

. This turns fructose 6-phosphate into glucosamine-6-phosphate. In step two, an acetyl group is transferred from acetyl CoA to the amino group on the glucosamine-6-phosphate creating N-acetyl-glucosamine-6-phosphate. In step three of the synthesis process, the N-acetyl-glucosamine-6-phosphate is isomerized, which will change N-acetyl-glucosamine-6-phosphate to N-acetyl-glucosamine-1-phosphate.

In step four, the phosphate-N-acetyl-glucosamine-1-phosphate, which is now a mono phosphate, attacks UTP. Uridine triphosphate, which is a pyrimidine
Pyrimidine
Pyrimidine is a heterocyclic aromatic organic compound similar to benzene and pyridine, containing two nitrogen atoms at positions 1 and 3 of the six-member ring...

 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...

, has the ability to act as an energy source. When UDP
Uridine diphosphate
Uridine diphosphate, abbreviated UDP, is a nucleoside diphosphate. It is an ester of pyrophosphoric acid with the nucleoside uridine. UDP consists of the pyrophosphate group, the pentose sugar ribose, and the nucleobase uracil.-See also:* Nucleoside...

 is used as an energy source, it gives off an inorganic phosphate. In this particular reaction after the monophosphate has attacked the UTP, a phosphate is given off as pyrophosphate, an inorganic phosphate, and is replaced by the monophosphate, creating UDP-Nacetylglucosamine (2,4. This initial stage, is used to create the precursor for the NAG in peptidoglycan.

In step 5, some of the UDP-Nacetylglucosamine (UDP-GlcNAc) is converted to UDP-MurNAc (UDP-N acetylmuramic acid) by the addition of a lactyl group to the glucosamine. Also in this reaction, C3 hydroxyl group will remove a phosphate form the alpha carbon of phosphenol pyruvate. This creates what is called an enol derivative that will be reduced to a “lactyl moiety” by NADPH in step six.

In step 7, the UDP –MurNAc is converted to UDP-MurNAC pentapeptide by the addition of five different amino acids as well as the dipeptide D-alanyl-D-alanine. Each of these reactions requires the energy source ATP. This is all referred to as Stage one.

Stage two is occurs in the cytoplasmic membrane. It is in the membrane where a lipid carrier called bactoprenol carries peptidoglycan precursors through the cell membrane. Bactoprenol will attack the UDP-MurNAc penta, creating a PP-MurNac penta, which is now a lipid. UDP-GlcNAc is then transformed into MurNAc, creating Lipid-PP-MurNAc penta-GlcNAc, a disaccharide, also a precursor to peptidoglycan. How this molecule is transported through the membrane is still not understood. However, once it is there, it is added to the growing glycan chain. The next reaction is known as tranglycosylation. In the reaction, the hydroxyl group of the GlcNAc will attach to the MurNAc in the glycan, which will displace the lipid-PP from the glycan chain. The enzyme responsible for this is transglycosylase.

External links

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