Chapter 25 Amino Acids, Peptides, and Proteins Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display. 4

25.1 Classification of Amino Acids 4

Fundamentals Amino acids are compounds that contain both an —NH2 group and a —CO2H group, but these groups are actually present in each amino acid as —NH3+ and —CO2– respectively. Amino acids are classified as , , , etc. amino acids according the carbon that bears the amino nitrogen.

Examples: Amino Acids + NH3  – CO2 + – H3NCH2CH2CO2  + – An -amino acid that is an intermediate in the biosynthesis of ethylene.  + H3NCH2CH2CO2 – A -amino acid that is one of the structural units present in coenzyme A.  + H3NCH2CH2CH2CO2 – A -amino acid involved in the transmission of nerve impulses. 

The 20 Key Amino Acids More than 700 amino acids occur naturally, but 20 of them are especially important. These 20 common amino acids are the ones used by organisms to synthesize proteins. All of them are -amino acids. They differ from one another with respect to the group (side chain) attached to the  carbon. These 20 are listed in Table 25.1.

Table 25.1 C O – R H H3N + The 20 amino acids obtained from hydrolysis of proteins vary according to R (the side chain). The properties of the amino acids also vary as the structure of R varies. Major differences among side chains: Size, shape and electronic characteristics.

Table 25.1 General ways of classifying a-amino acid side chains: nonpolar side chains polar uncharged side chains acidic side chains basic side chains aromatic side chains side chains containing an OH side chains containing an S

Table 25.1 C O – H H3N + Glycine (Gly or G) Glycine is the simplest amino acid. It is the only one in the table that is achiral. In all of the other amino acids in the table the  carbon is a chiral center.

Table 25.1 C O – CH3 H H3N + C O – CH(CH3)2 H H3N + Alanine Valine (Ala or A) (Val or V) Alanine and valine have alkyl groups as side chains, which are nonpolar and hydrophobic.

Table 25.1 H O H O + + – – H3N C C O H3N C C O CH2CH(CH3)2 CH3CHCH2CH3 Leucine Isoleucine (Leu or L) (Ile or I) Leucine, and isoleucine also have alkyl groups as side chains, which are nonpolar and hydrophobic.

Table 25.1 H O + – H3N C C O CH3SCH2CH2 Methionine (Met or M) The side chain in methionine is nonpolar, but the presence of sulfur makes it somewhat polarizable.

Table 25.1 C O – CH2 H H2N + H2C C H2 Proline (Pro or P) Proline is the only amino acid that contains a secondary amine function. Its side chain is nonpolar and cyclic.

Table 25.1 C O – CH2 H H3N + C O – CH2 H H3N + OH Phenylalanine Tyrosine (Phe or F) (Tyr or Y) The side chain in phenylalanine (nonpolar) is a benzyl group; the tyrosine side chain is similar to that of phenylalanine but has a phenolic -OH and can hydrogen bond.

Table 25.1 C O – CH2 H H3N + N Tryptophan (Trp or W) The side chain in tryptophan (a nonpolar amino acid) is larger and more polarizable than the benzyl group of phenylalanine.

Table 25.1 H O H O + + – – H3N C C O H3N C C O CH2OH CH3CHOH Serine Threonine (Ser or S) (Thr or T) The —OH side chain in serine and threonine can be involved in hydrogen bonding but is somewhat more crowded in threonine than in serine.

Table 25.1 H O + – H3N C C O CH2SH Cysteine (Cys or C) The side chains of two remote cysteines can be joined by forming a covalent S—S bond.

Table 25.1 C O – H H3N + H2NCCH2 C O – H H3N + H2NCCH2CH2 Asparagine Glutamine (Asn or N) (Gln or Q) The side chains of asparagine and glutamine terminate in amide functions that are polar and can engage in hydrogen bonding.

Table 25.1 C O – H H3N + OCCH2 C O – H H3N + OCCH2CH2 Aspartic Acid Glutamic Acid (Asp or D) (Glu or E) Aspartic acid and glutamic acid side chains exist as their conjugate bases at biological pH. They are negatively charged and can form ionic bonds with positively charged species.

Table 25.1 H O + – H3N C C O Lysine + (Lys or K) CH2CH2CH2CH2NH3 Lysine and arginine (next slide) side chains exist as their conjugate acids at biological pH. They are positively charged and can form ionic bonds with negatively charged species.

Table 25.1 H O + – Arginine H3N C C O (Arg or R) CH2CH2CH2NHCNH2 + NH2 Arginine has the most basic side chain of the 20 common amino acids (pKa ~12.5).

Table 25.1 H O + – H3N C C O Histidine (His or H) CH2 NH N Histidine is a basic amino acid, but less basic than lysine and arginine. Histidine can interact with metal ions and can help move protons from one site to another.

25.2 Stereochemistry of Amino Acids 4

Configuration of -Amino Acids Glycine is achiral. All of the other amino acids in proteins have the L-configuration at the carbon. H3N + H R CO2 – The convnention for drawing Fischer projections of the amino acids is as shown above.

25.3 Acid-Base Behavior of Amino Acids 4

Recall While their name implies that amino acids are compounds that contain an —NH2 group and a —CO2H group, these groups are actually present as —NH3+ and —CO2– respectively. How do we know this ? Logic, of course, says that acids protonate bases.

The properties of glycine: high melting point: (when heated to 233°C it decomposes before it melts). solubility: soluble in water; not soluble in nonpolar solvent. These properties are: O OH H2NCH2C •• • • – H3NCH2C + more consistent with this than this.

called a zwitterion or dipolar ion Properties of Glycine This ionized form is called a zwitterion or dipolar ion – • • O H3NCH2C •• + This is true for all of the -amino acids.

Acid-Base Properties of Glycine The zwitterionic structure of glycine also follows from considering its acid-base properties. A good way to think about this is to start with the structure of glycine in strongly acidic solution, say pH = 1. At pH = 1, glycine exists in its protonated form (a monocation). O OH H3NCH2C + •• • •

Acid-Base Properties of Glycine Now ask yourself "As the pH is raised, which is the first proton to be removed ? Is it the proton attached to the positively charged nitrogen, or is it the proton of the carboxyl group ?" You can choose between them by estimating their respective pKas. typical ammonium ion: pKa ~9 typical carboxylic acid: pKa ~5 O OH H3NCH2C + •• • •

Acid-Base Properties of Glycine The more acidic proton belongs to the CO2H group. It is the first one removed as the pH is raised. Therefore, the more stable neutral form of glycine is the zwitterion. typical carboxylic acid: pKa ~5 O OH H3NCH2C + •• • • – • • O H3NCH2C •• +

Acid-Base Properties of Glycine The measured pKa of glycine is 2.34. Glycine is stronger than a typical carboxylic acid because the positively charged N acts as an electron-withdrawing, acid-strengthening substituent on the  carbon. Glycine pKa is actually 2.34. O OH H3NCH2C + •• • • typical carboxylic acid: pKa ~5

Acid-Base Properties of Glycine A proton attached to N in the zwitterionic form of nitrogen can be removed as the pH is increased further. – • • O H3NCH2C •• + – • • O H2NCH2C •• HO – The pKa for removal of this proton is 9.60. This value is about the same as that for NH4+ (9.3) but less than that of a primary amine.

Isoelectric Point (pI) OH H3NCH2C + •• • • The pH at which the concentration of the zero net charge form is a maximum is called the isoelectric point. Its numerical value is the average of the two pKas. The pI of glycine is 5.97. pKa = 2.34 – • • O H3NCH2C •• + pKa = 9.60 – • • O H2NCH2C ••

Acid-Base Properties of Amino Acids One way in which amino acids differ is in respect to their acid-base properties. This is the basis for certain experimental methods for separating and identifying them. Just as important, the difference in acid-base properties among various side chains affects the properties of the proteins that contain them. Table 25.2 gives pKa and pI values for amino acids with neutral side chains.

Table 25.2 Amino Acids with Neutral Side Chains – H H3N + pKa1 = 2.34 pKa2 = 9.60 pI = 5.97 Glycine

Table 25.2 Amino Acids with Neutral Side Chains – CH3 H H3N + pKa1 = 2.34 pKa2 = 9.69 pI = 6.00 Alanine

Table 25.2 Amino Acids with Neutral Side Chains – CH(CH3)2 H H3N + pKa1 = 2.32 pKa2 = 9.62 pI = 5.96 Valine

Table 25.2 Amino Acids with Neutral Side Chains pKa1 = 2.36 pKa2 = 9.60 pI = 5.98 + – Leucine H3N C C O CH2CH(CH3)2

Table 25.2 Amino Acids with Neutral Side Chains – CH3CHCH2CH3 H H3N + pKa1 = 2.36 pKa2 = 9.60 pI = 6.02 Isoleucine

Table 25.2 Amino Acids with Neutral Side Chains pKa1 = 2.28 pKa2 = 9.21 pI = 5.74 + – Methionine H3N C C O CH3SCH2CH2

Table 25.2 Amino Acids with Neutral Side Chains – CH2 H H2N + H2C C H2 pKa1 = 1.99 pKa2 = 10.60 pI = 6.30 Proline

Table 25.2 Amino Acids with Neutral Side Chains – CH2 H H3N + pKa1 = 1.83 pKa2 = 9.13 pI = 5.48 Phenylalanine

Table 25.2 Amino Acids with Neutral Side Chains – CH2 H H3N + N pKa1 = 2.83 pKa2 = 9.39 pI = 5.89 Tryptophan

Table 25.2 Amino Acids with Neutral Side Chains – H H3N + H2NCCH2 pKa1 = 2.02 pKa2 = 8.80 pI = 5.41 Asparagine

Table 25.2 Amino Acids with Neutral Side Chains – H H3N + H2NCCH2CH2 pKa1 = 2.17 pKa2 = 9.13 pI = 5.65 Glutamine

Table 25.2 Amino Acids with Neutral Side Chains pKa1 = 2.21 pKa2 = 9.15 pI = 5.68 + – Serine H3N C C O CH2OH

Table 25.2 Amino Acids with Neutral Side Chains pKa1 = 2.09 pKa2 = 9.10 pI = 5.60 + – Threonine H3N C C O CH3CHOH

Table 25.2 Amino Acids with Neutral Side Chains – CH2 H H3N + OH pKa1 = 2.20 pKa2 = 9.11 pI = 5.66 Tyrosine

Table 25.2 Amino Acids with Ionizable Side Chains – H H3N + OCCH2 pKa1 = 1.88 pKa2 = 9.60 pKa* = 3.65 pI = 2.77 Aspartic acid For amino acids with acidic side chains, pI is the average of pKa1 and pKa*.

Table 25.2 Amino Acids with Ionizable Side Chains – H H3N + OCCH2CH2 pKa1 = 2.19 pKa2 = 9.67 pKa* = 4.25 pI = 3.22 Glutamic acid

Table 25.2 Amino Acids with Ionizable Side Chains pKa1 = 2.18 pKa2 = 8.95 pKa* = 10.53 pI = 9.74 + – H3N C C O + CH2CH2CH2CH2NH3 Lysine For amino acids with basic side chains, pI is the average of pKa2 and pKa*.

Table 25.2 Amino Acids with Ionizable Side Chains pKa1 = 2.17 pKa2 = 9.04 pKa* = 12.48 pI = 10.76 + – H3N C C O CH2CH2CH2NHCNH2 + NH2 Arginine

Table 25.2 Amino Acids with Ionizable Side Chains pKa1 = 1.82 pKa2 = 6.00 pKa* = 9.17 pI = 7.59 + – Histidine H3N C C O CH2 NH N

25.4 Synthesis of Amino Acids

1. From -Halo Carboxylic Acids CH3CHCOH Br O CH3CHCO NH3 O + – (65-70%) NH4Br H2O + 2NH3

2. The Strecker Synthesis CH3CH O NH4Cl CH3CHC NH2 N NaCN CH3CHCO NH3 O + – (52-60%) 1. H2O, HCl, heat 2. HO– Hydrolysis of the nitrile

3. Using Diethyl Acetamidomalonate OCH2CH3 H O CH3CH2O CH3CNH Can be substituted in the same manner as diethyl malonate (Section 20.11). Also, phthalimidomalonate can be used in place of acetamidomalonate as in the Gabriel Synthesis.

Example O CH3CH2OCCCOCH2CH3 CH3CNH H O 1. NaOCH2CH3 2. C6H5CH2Cl O Alkylation of malonate 2. C6H5CH2Cl O CH3CH2OCCCOCH2CH3 CH2C6H5 CH3CNH (90%) O

Example O CH3CH2OCCCOCH2CH3 CH3CNH CH2C6H5 O O HCCOH CH2C6H5 H3N + O O HBr, H2O, heat Hydrolysis of ester and amide –CO2 O O (65%) HOCCCOH An  amino acid H3N CH2C6H5 +

25.5 Reactions of Amino Acids 4

1. Acylation of Amino Group The amino nitrogen of an amino acid can be converted to an amide with the customary acylating agents. O CH3COCCH3 O H3NCH2CO – + + CH3CNHCH2COH O (89-92%)

2. Esterification of Carboxyl Group The carboxyl group of an amino acid can be converted to an ester. The following illustrates Fischer esterification of alanine. O H3NCHCO – + CH3 + CH3CH2OH HCl (90-95%) O H3NCHCOCH2CH3 + CH3 – Cl

3. Ninhydrin Reaction Amino acids are detected by the formation of Rhueman’s purple on treatment with ninhydrin. OH O O H3NCHCO – + R + O N – O RCH + CO2 + H2O +

25.6 Some Biochemical Reactions of Amino Acids 4

Decarboxylation Decarboxylation is a common reaction of -amino acids. Two examples are given below. + + H3NCH2CH2CH2CO2 – – –CO2, enzymes H3NCHCH2CH2CO2 – CO2 L-glutamic acid -aminobutyric acid (GABA) CH2CHCO2 – NH3 + N H N L-histidine CH2CH2 NH2 N H N histamine –CO2, enzymes

Neurotransmitters – CO2 OH CO2 – H H3N + The chemistry of the brain and central nervous system is affected by neurotransmitters. Several important neurotransmitters are biosynthesized from L-tyrosine. L-Tyrosine

Neurotransmitters – CO2 The common name of this compound is L-DOPA. It occurs naturally in the brain. It is widely prescribed to reduce the symptoms of Parkinsonism. + H3N H H H HO OH L-3,4-Dihydroxyphenylalanine

Neurotransmitters H Dopamine is formed by decarboxylation of L-DOPA. H2N H H H HO OH Dopamine

Neurotransmitters H H H2N H CH3NH H H OH H OH HO HO OH OH Norepinephrine Epinephrine

25.7 Peptides 4

Peptides Peptides are compounds in which an amide bond links the amino group of one -amino acid and the carboxyl group of another. An amide bond of this type is often referred to as a peptide bond. The amino acids in a peptide are called residues. Since a water was removed to make the peptide bond each residue does not represent a complete amino acid.

Alanylglycine CH3 O C + H – H3N O C H H3N + – Alanine Glycine CH3 O C H3N + H N – Two -amino acids are joined by a peptide bond in alanylglycine. It is a dipeptide.

Alanylglycine CH3 O C H3N + H N – N-terminus C-terminus Also written as: Ala—Gly or AG Peptides are always drawn with the N-terminus on the left and the C-terminus on the right. Residues are numbered from N-term to C-term.

Alanylglycine and glycylalanine are constitutional isomers CH3 O C H3N + H N – Alanylglycine Ala—Gly AG H O C H3N + N CH3 – Glycylalanine Gly—Ala GA

Alanylglycine CH3 O C H3N + H N – The peptide bond is characterized by a planar geometry. The carbonyl O and the amide H are anti to each other. The six atoms in the box are coplanar.

Higher Peptides Peptides are classified according to the number of amino acids linked together, similar to the saccharides, e.g.: dipeptides, tripeptides, tetrapeptides, etc. Leucine enkephalin (next slide) is an example of a pentapeptide.

Tyr—Gly—Gly—Phe—Leu YGGFL Leucine Enkephalin Tyr—Gly—Gly—Phe—Leu YGGFL

Oxytocin is a cyclic nonapeptide. Ile—Gln—Asn Tyr Cys S Cys—Pro—Leu—GlyNH2 1 2 3 4 5 6 7 8 9 C-terminus N-terminus Oxytocin is a cyclic nonapeptide. Instead of having its amino acids linked in an extended chain, two cysteine residues are joined by an S—S bond.

Oxytocin S—S bond An S—S bond between two cysteines is often referred to as a disulfide bridge.

25.8 Introduction to Peptide Structure Determination 4

Primary Structure The primary structure of a peptide or protein is its specific sequence of amino acids including any disulfide linkages. A general strategy for determining primary structure is given on the next slide.

Classical Strategy (Sanger) 1. Determine what amino acids are present and their molar ratios (amino acid composition). 2. Cleave the peptide into smaller fragments, and determine the amino acid composition of each smaller fragment. 3. Identify the N-terminus and C-terminus in the parent peptide and in each fragment. 4. Organize the information so that the sequences of small fragments can be overlapped to reveal the full sequence.

25.9 Amino Acid Analysis 4

Amino Acid Analysis Acid-hydrolysis of a peptide gives a mixture of amino acids (heat at 100o in 6 M HCl for 24 hr). The mixture is separated by ion-exchange chromatography. This method depends on the differences in isoelectric point (pI) among the various amino acids. Amino acids are detected using ninhydrin. An automated analyzer requires only 10-1 to 101 micrograms (μg) of peptide.

25.10 Partial Hydrolysis of Peptides 4

Partial Hydrolysis of Peptides and Proteins Acid-hydrolysis of the peptide as mentioned previously cleaves all of the peptide bonds. Partial hydrolysis cleaves some, but not all, of the peptide bonds and yields smaller peptides. These small fragments are then separated and the amino acids present in each fragment determined. Enzyme-catalyzed cleavage is one method used to produce cleavages.

Partial Hydrolysis of Peptides and Proteins Partial acid hydrolysis is performed using 6 N HCl at 100o for 30 minutes or at 37o for 2-3 days or at lower acid concentrations, etc. Enzymes that catalyze the hydrolysis of peptide bonds are generally called peptidases, proteases, or proteolytic enzymes, e.g. trypsin, -chymotrypsin, sa protease, etc.

Trypsin Trypsin is selective for cleaving the peptide bond to the carboxyl group of lysine or arginine. NHCHC O R' R" R lysine or arginine

Chymotrypsin Chymotrypsin is selective for cleaving the peptide bond to the carboxyl group of amino acids with an aromatic side chain. NHCHC O R' R" R phenylalanine, tyrosine or tryptophan

SA Protease SA Protease is selective for cleaving the peptide bond to the carboxyl group of Asp or Glu. NHCHC O R' R" R aspartic or glutamic

Carboxypeptidase Carboxypeptidase is selective for cleaving the peptide bond to the C-terminal amino acid. protein H3NCHC O R + NHCHCO – C

25.11 End Group Analysis 4

End Group Analysis Amino sequence is ambiguous unless we know whether to read it left-to-right or right-to-left. One needs to know the identity of the N-terminal and C-terminal amino acids. The C-terminal amino acid can be determined by carboxypeptidase-catalyzed hydrolysis. Several chemical methods have been developed for identifying the N-terminus. They depend on the fact that the amino N at the terminus is more nucleophilic than any of the amide nitrogens.

Sanger's Method The key reagent in Sanger's method for identifying the N-terminus is 1-fluoro-2,4-dinitrobenzene (FDNB). 1-Fluoro-2,4-dinitrobenzene is very reactive toward nucleophilic aromatic substitution (Chapter 12). F O2N NO2

Sanger's Method 1-Fluoro-2,4-dinitrobenzene reacts with the amino nitrogen of the N-terminal amino acid. F O2N NO2 NHCH2C NHCHCO CH3 NHCHC CH2C6H5 H2NCHC O CH(CH3)2 – + O2N NO2 NHCH2C NHCHCO CH3 NHCHC CH2C6H5 O CH(CH3)2 –

Sanger's Method Acid hydrolysis cleaves all of the peptide bonds leaving a mixture of amino acids, only one of which (the N-terminus) bears a 2,4-DNP group. O2N NO2 NHCH2C NHCHCO CH3 NHCHC CH2C6H5 O CH(CH3)2 – H3O+ O O2N NO2 NHCHCOH CH(CH3)2 H3NCHCO– CH3 + H3NCH2CO– O CH2C6H5

25.13 The Edman Degradation and Automated Sequencing of Peptides 4

Edman Degradation 1. Another method for determining N-terminal amino acid. 2. This method sequentially cleaves one residue at a time from the N-terminus. Using the automated method one can usually determine the first 20 or so amino acids from the N-terminus. 3. Only about 10-10 g of sample is needed.

Edman Degradation The key reagent in the Edman degradation is phenyl isothiocyanate. The carbon atom between the N and S is very electrophilic and is attacked by the N-term –NH2 of the peptide. N C S phenyl isothiocyanate

Edman Degradation peptide H3NCHC O R + NH C6H5N C S + peptide C6H5NHCNHCHC O R NH S

Edman Degradation peptide C6H5NHCNHCHC O R NH S The initial product is a phenylthiocarbamoyl (PTC) derivative. The PTC derivative is then treated with HCl in an anhydrous solvent. The N-terminal amino acid is cleaved from the remainder of the peptide.

Edman Degradation peptide C6H5NHCNHCHC O R NH S HCl C6H5NH C S N CH R O peptide H3N + + The product is a thiazolone which rearranges to a phenylthiohydantoin (PTH) derivative.

Edman Degradation C6H5NH C S N CH R O peptide H3N + + C N HN CH R O S C6H5 The PTH derivative is isolated and identified. The remainder of the peptide is subjected to a second Edman degradation. phenylthiohydantoin

25.14 The Strategy of Peptide Synthesis

General Considerations Making peptide bonds between amino acids is not difficult. The challenge is connecting amino acids in the correct sequence. Random peptide bond formation in a mixture of phenylalanine and glycine, for example, four dipeptides could be formed. Phe—Phe Gly—Gly Phe—Gly Gly—Phe

N-Protected phenylalanine General Strategy 1. The number of possibilities is limited by "protecting" the nitrogen of one amino acid and the carboxyl group of the other. N-Protected phenylalanine C-Protected glycine NHCHCOH CH2C6H5 O X H2NCH2C Y

General Strategy 2. Couple the two protected amino acids. NHCHCOH CH2C6H5 O X H2NCH2C O Y NHCH2C O Y NHCHC CH2C6H5 X

General Strategy 3. Deprotect the amino group at the N-terminus and the carboxyl group at the C-terminus. NHCH2C O Y NHCHC CH2C6H5 X NHCH2CO O H3NCHC CH2C6H5 + – Phe-Gly

25.17 Peptide Bond Formation 4

Forming Peptide Bonds The two major methods are: 1. coupling of suitably protected amino acids using N,N'-dicyclohexylcarbodiimide (DCCI) 2. via an active ester of the N-terminal amino acid. C6H11N C NC6H11 Dicyclohexylcarbodiimide The central C is very electrophilic.

DCCI-Promoted Coupling ZNHCHCOH CH2C6H5 O H2NCH2COCH2CH3 O + DCCI, chloroform ZNHCHC CH2C6H5 O NHCH2COCH2CH3 (83%) Overall reaction:

Mechanism of DCCI-Promoted Coupling ZNHCHCOH CH2C6H5 O + C6H11N C NC6H11 Oxygen of the acid group attacks DCCI which activates the C=O. CH2C6H5 O C6H11N C H OCCHNHZ

Mechanism of DCCI-Promoted Coupling CH2C6H5 O C6H11N C H OCCHNHZ H2NCH2COCH2CH3 O + Free –NH2 of another amino acid attacks the activated C=O. C6H11N C C6H11NH H O + ZNHCHC CH2C6H5 NHCH2COCH2CH3 Dicyclohexylurea New peptide

25.19 Primary and Secondary Structures of Peptides and Proteins 4

Levels of Protein Structure Primary structure = the amino acid sequence plus disulfide links. Secondary structure = conformational relationship between nearest neighbor amino acids.  helix  pleated sheet

Secondary Protein Structure The -helix and pleated  sheet are both characterized by: Planar geometry of peptide bond Anti conformation of main chain Hydrogen bonds between N—H and O=C

Pleated  Sheet Shown is a  sheet of protein chains composed of alternating glycine and alanine residues. Adjacent chains are antiparallel. Hydrogen bonds between chains. van der Waals forces produce pleated effect.

Pleated  Sheet  Sheet is most commonly seen with amino acids having small side chains (glycine, alanine, serine). 80% of fibroin (main protein in silk) is repeating sequence of —Gly—Ser—Gly—Ala—Gly—Ala—.  Sheet is flexible, but resists stretching.

 Helix Shown is an  helix of a protein in which all of the amino acids are L-alanine. Helix is right-handed with 3.6 amino acids per turn. Hydrogen bonds are within a single chain. Protein of muscle (myosin) and wool (-keratin) contain large regions of -helix. Chain can be stretched.

25.20 Tertiary and Quaternary Structures of Polypeptides and Proteins 4

Tertiary Structure Refers to overall shape (how the chain is folded). Fibrous proteins (hair, tendons, wool) have elongated shapes. Globular proteins are approximately spherical. Most enzymes are globular proteins. An example is carboxypeptidase.

Protein Quaternary Structure Some proteins are assemblies of two or more chains (3o subunits). The association of these subunits is called the quaternary structure. Hemoglobin, for example, isa tetramer consisting of 4 subunits. It has 2  chains (identical) and 2  chains (also identical). Each subunit contains one heme and each is about the size of myoglobin (monomeric).

End of Chapter 25 Amino Acids, Peptides, and Proteins 4