MM 4 _prorems!“5) We have already stated that « protein is a linear chain, built from 20 amino acids. (A few rared’s occur occasionally, but we will not discuss them.) ‘The chain contains of the order of 100-200 amino acid Of particular interest are the globular proteins, which act, for instance, as enzynes (catalyse), These proteins, in the proper solvent, fold into the final protein, as sketched in Fig. 1.1. PRIMARY Mprgsttaglly Te | — TeRTiany ‘STRUCTURE Fig. 141 The Linear polypeptide chain (primary sequence) folds into the final tertiary structur In this chapter we will describe the building blocks of proteins and make sone remarks about protein structure. Lebninger, Vol'kenshtein, Chapter 5. Stryer, Part 1. 4H, Neurath, The Proteins, Acadenic Pret E, Schulz and K. H. Schirmer, Princtples of Protein Structur: Springer, New York, 1979. Chapters 3-7. » mlti-volume,12 4.1 Amino Acids, the Building Blocks ‘The building blocks from which proteins are constructed are the amino acids. To a physicist, such complex organic molecules are often # nightmare. We suggest forgetting at the beginning that they are organic molecules and simply consider them building blocks with specified propertis ‘As they are used over and over again, their properteis become fantliar and they lose their intimidating character. All amino acids are built around a carbon atom. Two of the four ligand positions (valences) connect the amino acid to the other building blocks in the chain, one (the “eidechain") produces the characteristic features of a particular amino acid, and the fourth carries a hydrogs atom. The general structure thus ts shown in Fig. 2. Ris the residve that determines the R cooH carboxyl Characteristic . ~~ : i Nw residue (side chain) OK Links a ogee Figs 4.2 General structure of an amino acid. nino (Nip) Amportant specific properties of the amino acid. ‘The individual building blocks in a protein are linked together by peptide bonds. ‘The bond has covalent character and is so strong that it is practically never broken by thermal effect: In the formation of peptide bonds, water is elminated and a bond is formed: COvH. -HNH + -CO-NH- + H)0, The resulting polypeptide chain thus looks as indicated in Fig. |-3. In consists of a backbone and two3 te +HyN—C, {Ctl oe backbone eet fe peptide bond Fig. {.3 A polypeptide chain is formed from individual amino acids through peptide bonds. radicals per amino acid residue. The backbone is non-specific; the entire specificity is in the radicals, In addition to the components shown, proteins contain two endgroups the terminal carboxyl C0) denoted by -C the terminal amino wij denoted by -N The twenty common amino acide are given in Table }.1.M4 Table {.1 Properti¢ of protein building blocks. The length (L) 1s for the eide chain only. The molecular weight is for the entire amino acid - eubtract 17.9 to obtain molecular weight of residue. ‘The polarity indicates whether the amino acid is nonpolar (NP) or polar with a net positive, negative, or neutral charge at pH = 6. case ee = Seecie 1. a nino city al Ge rata BER) ET pines Ho pte a pe Gag et age ceo ttyl : Aowise AN OS 0 CRO x a a ee) > coe oh mak eee ¢ Frei pater tue WG 3 omens cw 0 - ceed gia leat si cieatietittts ¢ files eee ue cg ees oe eg bmn ME ass ow oS z tee uv mas L bee us sags Son Og baie ES WS 0 &® ESEE™ Ff poo. Wig tg Ee 3 Roo 6 ie [oS ? sme oe gS § ihe RIB = ‘Tryptophan TR 204 081 NP nam @) Ww " tome rh ao ge wD x Perea vag Cie iereag eet 3 c1s The side chains are shown schematically in Fig. \.4- Tr Met 1 Ne on $8 s Se On pS cr G, , . cys Se tw Asn on od neg be S Oba : a Ce oN . yt We asp ow eng ta ore Fig. 1.4 (After Schulz and Schirmer) ‘The 20 standard amino acid side chains. For proline part of the main chain is inserted. All other side chains are shown as they emerge from the C,-atom in the main chain. The residue names are given as three-letter symbofs. Atom naues are those given in the IUPAC- US recommendations of 1969. The main chain in Pro is indicated by solidly drawn bonds. All C,atons are black.In general, one classed; the amino acide into four groups: I, Amino acids with nonpolar (hydrophobic) radicals. ‘These amino acids are less soluble in water than the polar amino acids. II, Amino acide with uncharged polar radicals. ‘The polar R groups of these amino acids can hydrogen-bond with water and they are thus more soluble in water than those of group I. IIL, Amino acids with negatively charged (acidic) R groups. The menbers of this class possess a negative charge at pH 6-7. IV. Amino acids with positively charged (basic) R groups. ‘The basic amino acids have a positive charge at pH 7. Histidine is a borderline case; at pl 7, only about 10% have a positive charge; at pil 6, the percentage 1s about 50. ‘An excellent discussion of the properties of each amino acid can be found in Schulz and Schirmer, ALL amino acids can exist in two different forms, related to by a mirror reflection (Fig. 1.5)+ coon COOK 4,<@ NHS WN CMs 4 4 D-Ala L-Ala Fig. \.5 D and L forms of alanine,a7 D and L stand for dextro (right) and levulo (left). The two forms rotate the polarization of light in different directions. In nature, only the Lramtno acids are biologically active. In the laboratory, both forms can be produced. Sone expetinents, probably wrong, provide food for speculation. Did the L doninance come about by accident or through a deeper cause? Neutrinos and beta particles emitted in the weak interaction have a handedness. Could this be the agent to produce predominantly left-handed amino acids? Could one of the two forms be energetically favored? (6) In describing a sequence, the various amino acids are designated either by a three-letter or by a one-letter abbreviation. The sbbreviations are Listed in Table 1.1. ‘The Primary Sequ Proteins consist of about 100 to 1000 amino acids bound together to fora a polypeptide chain, Investigation of the primary sequence already reveals fascinating features. Consider for instance the primaty sequence of cytochrome c, an electron transport enzyme. (R. E. Dickerson, Scientific ‘Averican, April 1972; reprinted in The Chemical Basis of Life). The primary sequence of this protein has been determined in @ large number of cases. Table \.2 gives part of the sequence for these. (The complete table can be found in Dickerson or in M. 0, Dayhoff, Atlas of Protein Sequence and Structure.) . For a review see L. Keazthelyi, “Origin of the Asymmetry of Biomolecules and Weak Interaction". Origins of Life 8, 299-340 (1977).1-8 Table 1.2 Partial Sequence of Cytochrome . ° 2 a Orzssseres OLzs4ser189 O1zsesered 123456709 sede en SEDISEIt ze wie OKT To -Vo@TRT Es SENG RCRUL CY. ERCRR DEVORE DYER GK ET FltaRkece ov Pll leet SSS SSE Ee We notice that this sedvondtranger atin hs chang verq URE in the course of fungi, plante, about 109 years. Cyt ¢ 1s essentially the same in bacteria, they are occupied dnvartant, some positions are In particular, and in humans. by exactly the came amino acid in every sequence. A mutation in such a position is lethal. The differences between any The table can be used to draw a family tree. differ by one for instance, Man and rhesus monkey, two chains are counted. ‘The difference table then provides us with a family tree. Table and residue, fam{ly tree are shown on the next page, in Fig. 1.6. 3m the following section, we will diecuss briefly a few simple proteins, to make the general discussion somewhat more specific.14 ec Tibr 27, hei latin Som ma Fig 1.6 THE FAMELy raze OF THE CYTOCHROMES C ‘The species differences shown in the table above left lead to a tree of family relatedness, Note that these ts no ascending hierarchy. From the viewpoint of a yeast (if had one, and therein lies a real if anthropocentric distinction), a moth, a man, and a bullfrog are equally far away, Note also how Provincial is the view that we usually take of the living kingdom. The differences between fungi fre greater than those between insects and vertebrates. Trem Dickerson 21.3. Some Typical Proteins Proteins perform an amazing number of functions and we only mention a major subdivision here between structural and functional proteins. Structural Proteins are more uniform and use repeated units, as in a mass-produced building. Functional proteins are tailor-made for a specific job, such as storing energy or matter (oxygen) or catalyzing a particular reaction. The basic building blocks are the sane, but they are used differently. Moreover, Ron-protein subunits are sometimes tncorporated into functional proteins. The non-polypeptide part is called the prosthelic group, the protein without it apoprotein, As shown in Fig. (.1, a protein first folds into a secondary and then into a tertiary structure. The geometry of the amino acids permit only a small number of secondary structures. Of these, two are most often used in nature, the alpha helix and the antiparallel beta pleated sheet. Their basic structures are shown in Fig. 1.7, Ankigamailel B pleatea sheet Fig. \.7 Alpha helix and antiparallel beta pleated sheet.=n Globular proteins are largely built from pieces of alpha helices, interrupted by groups that permit bending and twisting, and from beta pleated sheets. Structural proteins also use both units, but in a periodic arrangement. We sketch in the following some examples that we will use again in later discussions. 4 over and over again. In heme proteins, nature us 3.1. Heme Proteins. When nature discovers a good trick, it is used @ particular organic molecule, the heme group, embeds it into different proteins (“globins"), and with the protein modifies the properties of the heme group so that the entire system performs a given task. A heme protein thus looks schematically as sketched in Fig. (. Before discussing the heme group and some heme proteins in more detail, we list in Table /.3 a number of heme proteins with their functions. globin OPT EO Fig. (.8 A cross section through a heme protein.