Proteins peptide bond. How is a peptide bond formed in humans? Peptide bond formation
Proteins, their content in living matter and molecular weight
Proteins, their structure and properties
Of the organic substances of living matter, proteins, or proteins (from the Greek. protos- main, primary). The composition of organisms currently living on Earth contains about 1 trillion tons of proteins. Proteins make up 10–18% of the mass, for example, of an animal cell, i.e. half the dry weight of the cell.
There are at least several thousand protein molecules in each cell.
Proteins are high-molecular polymers (macromolecules) with a molecular weight of 6 thousand to 1 million and more. Compared to molecules of alcohol or organic acids, proteins look like giants. Thus, the molecular weight of insulin is 5700, egg albumin is 36,000, and myosin is 500,000.
The composition of proteins includes atoms C, H, O, N, S, P, sometimes Fe, Cu, Zn. To elucidate the chemical structure of proteins, knowledge of their elemental composition is not enough. For example, the empirical formula of hemoglobin - C 3032 H 4816 O 872 S 8 Fe 4 - does not say anything about the nature of the arrangement of atoms in the molecule. It is necessary to get acquainted with the structural features of protein molecules in more detail.
2. Proteins are non-periodic polymers. The structure and properties of amino acids
By their chemical nature, proteins are non-periodic polymers. The monomers of protein molecules are amino acids. In general, an amino acid can be called any compound containing both an amino group (–NH 2) and a group of organic acids - a carboxyl group (–COOH). The number of possible amino acids is very large, but proteins form only 20 so-called golden, or standard, amino acids (8 of them are essential, because they are not synthesized in animals and humans). It is the combination of these 20 amino acids that gives the whole variety of proteins. After a protein molecule is assembled, some amino acid residues in its composition can undergo chemical changes, so that up to 30 different amino acid residues can be found in “mature” proteins (but all proteins are built initially from only 20 anyway!).
The cell contains free amino acids that make up the amino acid pool, due to which new proteins are synthesized. This fund is replenished with amino acids that constantly enter the cell due to the breakdown of food proteins by digestive enzymes or the breakdown of their own storage proteins. Depending on the amino acid composition, proteins are complete, containing the entire set of amino acids, and incomplete, which lack some amino acids.
The general formula of amino acids is shown in the figure. The amino group -NH 2 is located on the left side of the formula, and the carboxyl group -COOH is located on the top. The -NH 2 group has basic properties, the -COOH group has acidic properties. Thus, amino acids are amphoteric compounds that combine the properties of an acid and a base.
Amino acids differ in their radicals (R), which can be a variety of compounds. This results in a wide variety of amino acids.
Amphoteric properties of amino acids due to their ability to interact with each other. Two amino acids are connected by a condensation reaction into one molecule by establishing a bond between the carbon of the acidic and nitrogen of the main groups with the release of a water molecule.
The link on the left is called peptide(from Greek. pepsis- digestion). This term reminds us that this bond is hydrolyzed by a digestive enzyme in the stomach. pepsin. By nature, the peptide bond is covalent.
The combination of two amino acids is called a dipeptide, three - a tripeptide, etc. An example of a tripeptide is a protein glutathione, consisting of residues of glycine, cysteine and glutamic acid. It is found in all living cells (especially a lot of it in the germ of wheat grain and yeast) and is actively involved in metabolism.
Glutathione
Basically, the proteins that make up living organisms include hundreds and thousands of amino acids (most often from 100 to 300), so they are called polypeptides. Amino acids in the composition of the protein polypeptide chain are called amino acid residues.
Peptides differ in number ( n), the nature, order, or sequence of their amino acid residues. They can be compared to words of different lengths, which are written using an alphabet consisting of 20 letters. From 20 amino acids, theoretically, 1020 possible chain variants can be obtained, each at least 10 amino acid residues long. Proteins isolated from living organisms are formed by hundreds and sometimes thousands of amino acid residues. This is the source of the infinite variety of protein molecules, which is an important prerequisite for the evolutionary process.
A peptide bond is a strong connection between fragments of two amino acids, which underlies the formation of linear structures of proteins and peptides. In such molecules, each amino acid (with the exception of the terminal ones) is connected to the previous and subsequent ones.
Depending on the number of links, peptide bonds can create dipeptides (consist of two amino acids), tripeptides (of three), tetrapeptides, pentapeptides, etc. Short chains (from 10 to 50 monomers) are called oligopeptides, and long chains are called polypeptides and proteins ( mol weight more than 10 thousand Yes).
Characterization of the peptide bond
A peptide bond is a covalent chemical bond between the first carbon atom of one amino acid and the nitrogen atom of another, resulting from the interaction of an alpha carboxyl group (COOH) with an alpha amino group (NH 2). In this case, the nucleophilic substitution of OH-hydroxyl for an amino group occurs, from which hydrogen is separated. As a result, a single C-N bond and a water molecule are formed.
Since the loss of some components (OH group and hydrogen atom) occurs during the reaction, peptide units are no longer called amino acids, but amino acid residues. Due to the fact that the latter contain 2 carbon atoms, the peptide chain alternates between C-C and C-N bonds, which form the peptide backbone. On the sides of it are amino acid radicals. The distance between carbon and nitrogen atoms varies from 0.132 to 0.127 nm, which indicates an indefinite bond.
A peptide bond is a very strong type of chemical interaction. Under standard biochemical conditions corresponding to the cellular environment, it does not undergo self-destruction.
The peptide bond of proteins and peptides is characterized by the property of coplanarity, since all the atoms involved in its formation (C, N, O and H) are located in the same plane. This phenomenon is explained by the rigidity (i.e., the impossibility of rotation of the elements around the bond) resulting from resonance stabilization. Within the amino acid chain, between the planes of the peptide groups, there are α-carbon atoms associated with radicals.
Configuration types
Depending on the position of the alpha carbon atoms relative to the peptide bond, the latter can have 2 configurations:
- "cis" (located on one side);
- "trans" (located on different sides).
The trans form is characterized by greater stability. Sometimes configurations are characterized by the arrangement of radicals, which does not change the essence, since they are associated with alpha carbon atoms.
Resonance phenomenon
The peculiarity of the peptide bond is that it is 40% double and can be found in three forms:
- Ketolic (0.132 nm) - C-N-bond is stabilized and completely single.
- Transitional or mesomeric - an intermediate form, has a partially indefinite character.
- Enol (0.127 nm) - the peptide bond becomes completely double, and the C-O connection becomes completely single. In this case, the oxygen acquires a partially negative charge, and the hydrogen atom acquires a partially positive charge.
This feature is called the resonance effect and is explained by the delocalization of the covalent bond between the carbon and nitrogen atom. In this case, the hybrid sp 2 orbitals form an electron cloud that propagates to the oxygen atom.
Peptide bond formation
Peptide bond formation is a typical polycondensation reaction that is thermodynamically unfavorable. Under natural conditions, the equilibrium is shifted towards free amino acids, therefore, for the implementation of the synthesis, a catalyst is required that activates or modifies the carboxyl group for easier leaving of the hydroxyl group.
In a living cell, the formation of a peptide bond occurs in the protein-synthesizing center, where specific enzymes act as a catalyst, working with the expenditure of energy from macroergic bonds.
Amino acids in the polypeptide chain are linked by an amide bond, which is formed between the α-carboxyl group of one and the α-amino group of the next amino acid (Fig. 1). The covalent bond formed between amino acids is called peptide bond. The oxygen and hydrogen atoms of the peptide group in this case occupy a transposition.
Rice. 1. Scheme of peptide bond formation.In each protein or peptide, one can distinguish: N-terminus a protein or peptide that has a free a-amino group (-NH2);
S-endhaving a free carboxyl group (-COOH);
Peptide backboneproteins, consisting of repeating fragments: -NH-CH-CO-; Amino acid radicals(side chains) (R1 and R2)- variable groups.
The abbreviated notation of the polypeptide chain, as well as protein synthesis in cells, necessarily begins at the N-terminus and ends at the C-terminus:
The names of the amino acids included in the peptide and forming a peptide bond have the endings -ill. For example, the tripeptide above is called threonyl-histidyl-proline.
The only variable part that distinguishes one protein from all the others is the combination of radicals (side chains) of the amino acids that make up it. Thus, the individual properties and functions of a protein are determined by the structure and sequence of amino acids in the polypeptide chain.
Polypeptide chains of various body proteins can include from a few amino acids to hundreds and thousands of amino acid residues. Their molecular weight (molecular weight) also varies widely. So, the hormone vasopressin consists of 9 amino acids, they say. mass 1070 kD; insulin - from 51 amino acids (in 2 chains), they say. mass 5733 kD; lysozyme - from 129 amino acids (1 chain), they say. mass 13 930 kD; hemoglobin - from 574 amino acids (4 chains), they say. mass 64,500 kD; collagen (tropocollagen) - from about 1000 amino acids (3 chains), they say. mass ~130,000 kD.
The properties and function of a protein depend on the structure and order of alternation of amino acids in the chain, a change in the amino acid composition can greatly change them. So, 2 hormones of the posterior pituitary gland - oxytocin and vasopressin - are nanopeptides and differ in 2 of 9 amino acids (in positions 3 and 8):
The main biological effect of oxytocin is to stimulate the contraction of the smooth muscles of the uterus during childbirth, and vasopressin causes water reabsorption in the renal tubules (antidiuretic hormone) and has a vasoconstrictive property. Thus, despite the great structural similarity, the physiological activity of these peptides and the target tissue they act on differ, i.e. replacement of only 2 of 9 amino acids causes a significant change in the function of the peptide.
Sometimes a very small change in the structure of a large protein causes suppression of its activity. So, the enzyme alcohol dehydrogenase, which breaks down ethanol in the human liver, consists of 500 amino acids (in 4 chains). Its activity among the inhabitants of the Asian region (Japan, China, etc.) is much lower than among the inhabitants of Europe. This is due to the fact that in the polypeptide chain of the enzyme, glutamic acid is replaced by lysine at position 487.
Interactions between amino acid radicals are of great importance in stabilizing the spatial structure of proteins; 4 types of chemical bonds can be distinguished: hydrophobic, hydrogen, ionic, disulfide.
Hydrophobic bonds arise between nonpolar hydrophobic radicals (Fig. 2). They play a leading role in the formation of the tertiary structure of the protein molecule.
Rice. 2. Hydrophobic interactions between radicals
Hydrogen bonds- are formed between polar (hydrophilic) uncharged groups of radicals having a mobile hydrogen atom, and groups with an electronegative atom (-O or -N-) (Fig. 3).
Ionic bonds are formed between polar (hydrophilic) ionic radicals having oppositely charged groups (Fig. 4).
Rice. 3. Hydrogen bonds between amino acid radicals
Rice. 4. Ionic bond between lysine and aspartic acid radicals (A) and examples of ionic interactions (B)
disulfide bond- covalent, formed by two sulfhydryl (thiol) groups of cysteine radicals located in different places of the polypeptide chain (Fig. 5). It is found in proteins such as insulin, the insulin receptor, immunoglobulins, etc.
Disulfide bonds stabilize the spatial structure of one polypeptide chain or link 2 chains together (for example, chains A and B of the insulin hormone) (Fig. 6).
Rice. 5. Formation of a disulfide bond.
Rice. 6. Disulfide bonds in the insulin molecule. Disulfide bonds: between cysteine residues of the same chain BUT(a), between chains BUT and AT(b). Numbers - position of amino acids in polypeptide chains.
Peptides- These are natural or synthetic compounds, the molecules of which are built from amino acid residues interconnected by peptide (peptide bridge), in essence, amide bonds.
Peptide molecules may contain a non-amino acid component. Peptides with up to 10 amino acid residues are called oligopeptides(dipeptides, tripeptides, etc.) Peptides containing more than 10 to 60 amino acid residues are classified as polypeptides. Natural polypeptides with a molecular weight of more than 6000 daltons are called proteins.
Nomenclature
The amino acid residue of a peptide that carries the α-amino group is called N-terminal, bearing a free -carboxyl group - C-terminal. The name of the peptide consists of a listing of the trivial names of amino acids, starting with the N-terminal. In this case, the suffix "in" changes to "il" for all amino acids, except for the C-terminal.
Examples
Glycylalanine or Gly-Ala
b) alanyl-seryl-aspargyl-phenylalanyl-glycine
or Ala - Ser - Asp - Phe - Gly. Here, alanine is the N-terminal amino acid and glutamine is the C-terminal amino acid.
Peptide classification
1. Homeric Hydrolysis produces only amino acids.
2. Heteromeric- during hydrolysis, in addition to -amino acids, non-amino acid components are formed, for example:
a) glycopeptides;
b) nucleopeptides;
c) phosphopeptides.
Peptides can be linear or cyclic. Peptides in which the bonds between amino acid residues are only amide (peptide) are called homogenous. If, in addition to the amide group, there are ester, disulfide groups, the peptides are called heterogeneous. Heterodetic peptides containing hydroxyamino acids are called peptolides. Peptides consisting of one amino acid are called homopolyamino acids. Those peptides that contain the same repeating sections (of one or more amino acid residues) are called regular. Heteromeric and heterodet peptides are called depsipeptides.
The structure of the peptide bond
In amides, the carbon-nitrogen bond is partially doubly bonded due to p,-conjugation of the NPE of the nitrogen atom and the carbonyl -bond (C-N bond length: in amides - 0.132 nm, in amines - 0.147 nm), therefore the amide group is planar and has trans configuration. Thus, the peptide chain is an alternation of flat fragments of the amide group and fragments of hydrocarbon radicals of the corresponding amino acids. In the latter, rotation around simple bonds is not difficult; this results in the formation of various conformers. Long chains of peptides form -helices and β-structures (similar to proteins).
Synthesis of peptides
During peptide synthesis, a peptide bond must be formed between the carboxyl group of one amino acid and the amine group of another amino acid. Two amino acids can form two dipeptides:
The above schemes are formal. For the synthesis of, for example, glycylalanine, it is necessary to carry out appropriate modifications of the initial amino acids (this synthesis is not considered in this manual).
Polypeptides are proteins that have an increased condensation degree. They are widely distributed among organisms of both plant and animal origin. That is, here we are talking about components that are mandatory. They are extremely diverse, and there is no clear line between such substances and ordinary proteins. If we talk about the diversity of such substances, then it should be noted that when they are formed, at least 20 amino acids of the protenogenic type are involved in this process, and if we talk about the number of isomers, then they can be infinite.
That is why protein-type molecules have so many possibilities that are practically limitless when it comes to their multifunctionality. So, it is understandable why proteins are called the main of all life that is on Earth. Proteins are also called one of the most complex substances that nature has ever formed, and they are also very unique. Just like protein, proteins contribute to the active development of living organisms.
Speaking as specifically as possible, we are talking about substances that are biopolymers based on amino acids containing at least hundreds of amino acid type residues. Moreover, there is also a division here - there are substances that belong to a low molecular weight group, they include only a few tens of amino acid residues, there are also substances that belong to high molecular weight groups, they contain much more such residues. A polypeptide is a substance that is really very diverse in its structure and organization.
Groups of polypeptides
All these substances are conditionally divided into two groups, with such a division, the features of their structure are taken into account, which have a direct impact on their functionality:
- The first group includes substances that differ in a typical protein structure, that is, this includes a chain of a linear type and directly amino acids. They are found in all living organisms, and substances with increased activity of the hormonal type are of the greatest interest here.
- As for the second group, here are those compounds whose structure does not have the most typical features for proteins.
What is a polypeptide chain
The polypeptide chain is a protein structure that includes amino acids, all of which have a strong connection with peptide-type compounds. If we talk about the primary structure, then we are talking about the simplest level of the structure of a protein-type molecule. This organizational form is characterized by increased stability.
When peptide bonds begin to form in cells, the carboxyl-type group of one amino acid first of all activates, and only then does an active connection with another similar group begin. That is, polypeptide chains are characterized by constantly alternating fragments of such bonds. There are a number of specific factors that have a significant impact on the shape of the primary type structure, but their influence is not limited to this. There is an active influence on those organizations of such a chain that have the highest level.
If we talk about the features of such an organizational form, then they are as follows:
- there is a regular alternation of structures belonging to the rigid type;
- there are sections that have relative mobility, they have the ability to rotate around the bonds. It is features of this kind that affect how the polypeptide chain fits in space. Moreover, various organizational moments can be carried out with peptide chains under the influence of many factors. There may be detachment of one of the structures, when the peptides form into a separate group and are separated from one chain.
Protein structure of secondary type
Here we are talking about a variant of chain folding in such a way that an ordered structure is organized, this becomes possible due to hydrogen bonds between groups of peptides of one chain with the same groups of another chain. If we take into account the configuration of such a structure, then it can be:
- Spiral type, this name came about due to its peculiar shape.
- Layered-folded type.
If we talk about a helical group, then this is such a protein structure that is formed in the form of a helix, which is formed without going beyond one chain of the polypeptide type. If we talk about the appearance, then it is in many ways similar to the usual electric spiral, which is in a tile that runs on electricity.
As for the layered-folded structure, here the chain is distinguished by a bent configuration, its formation is carried out on the basis of hydrogen-type bonds, and here everything is limited to the limits of one section of a particular chain.
