Amino acids, Peptides, and ProteinsBIOL420ada D. Son

OutlineWhat are proteins?Building blocksProperties of Amino AcidsUncommon Amino AcidsReactions of Amino Acids

Proteins are the most abundant biological macromolecules, occurring in all cells and all parts of cells.

Proteins also occur in great variety;

Proteins are the molecular instruments through which genetic information is expressed.Protein Basics

Protein BasicsProteinsare biologicalmacromolecules made ofamino acidsarranged in a linear chain and folded into varius 3D structures.The amino acids in apolymerchain are joined together by thepeptide bondsbetween thecarboxylandaminogroups of adjacent amino acidresiduesThe sequence of amino acids in a protein is defined by thesequenceof agene, which is encoded in thegenetic code

PROTEINSThe term protein was first used by the Dutch chemist Gerardus Mulder in 1838 to name a specific group of substances abundant in all plants and animals. The importance of proteins was correctly predicted by Mulder, who derived the name from the Greek word proteios, meaning primary or first rank.Now that the human genome sequence has been completed, we know to a high degree of accuracy the order of nucleotides in DNA. The challenge ahead is to understand the purpose of each and every protein product that is coded in the genome. We called this group of proteins the proteome; proteomics is the broad study of all cellular proteins. More specifically, proteomics has the following goals: classify and characterize all protein products coded by DNA, investigate regulation and expression levels (cellular concentrations and impact on health), determine the complete structure of each protein, study how proteins interact with one another and with other biomolecules, and identify the functional role of each.So, the question is what is protein?...

Protein BasicsProteins are polymers of amino acids, with each amino acid residue joined to its neighbour by a specific type of covalent bond.

An amino acid is any organic molecule with at least one carboxyl group (organic acid) and at least one amino group (organic base).

Several hundreds of different amino acids are known to be present in plant and animal cells. Only those 20, are genetically coded for incorporation into proteins.

Amino AcidspH = 7.4

ChiralityA chiral molecule is a type of molecule that lacks an internal plane of symmetry and has a non-superimposable mirror image. The feature that is most often the cause of chirality in molecules is the presence of an asymmetric carbon atomTwo mirror images of a chiral molecule are called enantiomers or optical isomers

Chirality

Chirality for Amino AcidsFor all the common amino acids except glycine, the -carbon is bonded to four different groups: a carboxyl group, an amino group, an R group, and a hydrogen atom.The -carbon atom is thus a chiral center. Because of the tetrahedral arrangement of the bonding orbitals around the -carbon atom, the four different groups can occupy two unique spatial arrangements, and thus amino acids have two possible stereoisomers. Since they are nonsuperimposable mirror images of each other, the two forms represent a class of stereoisomers called enantiomers. All molecules with a chiral center are also optically activethat is, they rotate plane-polarized light.

Determining theD/Lisomeric form of an Amino Acidthe "CORN" ruleThe groups: COOH, R, NH2 and H (where R is a variant carbon chain)are arranged around the chiral center carbon atom. Sighting with the hydrogen atom away from the viewer, if these groups are arranged clockwise around the carbon atom, then it is theD-form. If counter-clockwise, it is theL-form.

The D and L enantiomers for the amino acid, Alanine.

ChiralityIn Biological systems L-form of the amino acids is prefered.D-alanine and D-glutamate are first discovered in short peptides of cell walls of Gram-negative bacteria.D-valine is present in peptide antibiotics: valinomycine, actinomycin D, gramicidin A.D-aspartate is isolated in human teeth, eye lenses, erythrocytes and some tumors.D-serine is isolated from mammalian brain where it functions as neurotransmitter.

Amino Acids Can Be Classified by R GroupNonpolar, Aliphatic R Groups The R groups in this class of amino acids are nonpolar and hydrophobic.

Aromatic R Groups Phenylalanine, tyrosine, and tryptophan, with their aromatic side chains, are relatively nonpolar (hydrophobic). All can participate in hydrophobic interactions. The hydroxyl group of tyrosine can form hydrogen bonds.

Polar, Uncharged R Groups The R groups of these amino acids are more soluble in water, or more hydrophilic, than those of the nonpolar amino acids, because they contain functional groups that form hydrogen bonds with water.

Amino Acids Can Be Classified by R GroupPositively Charged (Basic) R Groups The most hydrophilic R groups are those that are either positively or negatively charged.

Negatively Charged (Acidic) R Groups The two amino acids having R groups with a net negative charge at pH 7.0 are aspartate and glutamate, each of which has a second carboxyl group.

Uncommon Amino Acids Also HaveImportant FunctionsIn addition to the 20 common amino acids, proteins may contain residues created by modification of common residues already incorporated into a polypeptide. Among these uncommon amino acids are:6-NMethyllysine is a constituent of myosin, a contractile protein of muscle. Another important uncommon amino acid is -carboxyglutamate, found in the bloodclotting protein prothrombin and in certain other proteins that bind Ca2 as part of their biological function.More complex is desmosine, a derivative of four Lys residues, which is found in the fibrous protein elastin.

www.ull.chemistry/uakron/biochem/0421st amino acidMammalian glutathione peroxidase enzyme contains selenocysteine.

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www.ull.chemistry/uakron/biochem/0422nd amino acidMonomethylamine methyltransferase enzyme of a freshwater bacteria contains this amino acid.

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Selenocysteine is a special case. This rare amino acid residue is introduced during protein synthesis rather than created through a postsynthetic modification. It contains selenium rather than the sulfur of cysteine. Actually derived from serine, selenocysteine is a constituent of just a few known proteins.

Some 300 additional amino acids have been found in cells. They have a variety of functions but are not constituents of proteins.

Ornithine and citrulline deserve special note because they are key intermediates (metabolites) in the biosynthesis of arginine and in the urea cycle.

Amino Acids Can Act as Acids and BasesWhen an amino acid is dissolved in water, it exists in solution as the dipolar ion, or zwitterion (German for hybrid ion). A zwitterion can act as either an acid (proton donor) or a base (proton acceptor):

Substances having this dual nature are amphoteric and are often called ampholytes (from amphoteric electrolytes).

A simple monoamino monocarboxylic -amino acid, such as alanine, is a diprotic acid when fully protonatedit has two groups, the -COOH group and the NH+3 group, that can yield protons.

Ionizable Groups

Titration of an amino acid

Two ionic forms of Histidine may be present in vivo. Which one would be predominant at a pH of 7.4? pH = pKa + log ( [A-]/ [HA] )

The amino acid cysteine has an SH (sulfhydryl) group on the side chain. This -SH group of cysteine can react under oxidizing conditions with an SH of another cysteine forming a disulfide bond. This covalent bonding between cysteines becomes important in protein three-dimensional structures.Two Cysteine residues react with an oxidizing agent to form Cystine containing a disulfide bond. A reducing agent AH2, causes the cleavage of the disulfide bond to reverse the reaction

Peptide Bond

Primary Structure

*thousands of different kinds, ranging in size from relatively small peptides to huge polymers with molecular weights in the millions, may be found in a single cell. Moreover, proteins exhibit enormous diversity of biological function and are the most important final products of the information pathways. **Overview of protein structure and function*The general structure for the 20 amino acids in proteins. The four groups are linked covalently to the carbon. The R side chains change depending on the type of the amino acid. The bottom structure shows the correct ionic structures at physiological pH.

****(a)The two stereoisomers of alanine, L- and D-alanine, are nonsuperimposable mirror images of each other (enantiomers). (b, c) Two different conventions for showing the configurations in space of stereoisomers. In perspectiveformulas (b) the solid wedge-shaped bonds project out of the plane of the paper, the dashed bonds behind it. In projection formulas (c) the horizontal bonds are assumed to project out of the plane of the paper, the vertical bonds behind. However, projection formulas are often used casually and are not always intended to portray a specific stereochemical configuration.

***********4-hydroxyproline, a derivative of proline, and 5-hydroxylysine, derived from lysine. The former is found in plant cell wall proteins, and both are found in collagen, a fibrous protein of connective tissues. *********