1

Madeline A. SheaProf. of Biochemistry4-450 BSB, 335-7885madeline-shea@uiowa.edu

99:163 Medical BiochemistryAmino Acids, Peptides & Antigens

For Lectures #1, #2

2

I. Welcome, Reading List & AnnouncementsII. Scientific Topics

A. Themes in BiochemistryB. Amino Acids

i. Basic Overviewii. Abbreviationsiii. Fundamental Propertiesiv. Titration Curve Examplesv. 3-D Representationsvi. Pre-biotic Synthesisvii. Amino Acid Isomers (L- and D- form)viii. Acid-Base Reactivityix. Amino Acid Sidechains

C. Peptides and Proteinsi. Protein Functionsii. Peptide Bonds & Structure Geometryiii. Antigens, Peptidesiv. Levels of Protein Structure

Outline of Handout #1

3

1. Know the names, 3-letter and 1-letter abbreviations for all20 common amino acids.

2. Recognize structures of amino acids as they exist at pH1.5, pH 7.0, and pH 11.0.

3. Identify the 20 common amino acid(s) that are:a) acidicb) basicc) aromaticd) have a carboxyl group in their side chainse) absorb UV light stronglyf) have an alpha nitrogen that is a 2o amine ( = an imine)g) is the smallest amino acid

4. Are all proteins polypeptides? Are all peptides proteins?What are special characteristics of the bond that connectsamino acids to make polypeptides?

Study Goals - Key Concepts

4

All biochemistry texts cover these topics.• Lippincott’s Review (3e or 4e)• Lehninger, Nelson and Cox (4e)• Berg, Tymoczko, Stryer (5e)• Devlin• Schaum’s Outline of Biochemistry

•MANY, many good websites includehttp://www.biology.arizona.edu/biochemistry/problem_sets/aa/aa.htmlhttp://bcs.whfreeman.com/biochem5

Suggested Textbooks

5

• People suffer and die from faulty bio-molecules.• Cystic fibrosis, Phenylketonuria, Sickle Cell, Lesch-Nyhan.

• Differences between humans and pathogens start here (providing clues tocures and diagnosis).• Interfering with cell walls vs. cell membranes

• Bio-molecules are early detectors and telltale reporters.• Tests for pregnancy, prostate cancer, heart attack, etc.

• Medicine in the “Genome-Lane”• requires working knowledge of gene-products.

• The same equations have the same solutions.• Bottom line: It will help you be a better physician.

• Window screens and clean water are essential for good health,but biochemistry will let you be the best doctors you can be,and make new connections between symptoms and causes!

• and it’s on “the boards”

Why Study Biochemistry?(aka Molecular Medicine)

6

• A winning recipe: come to class.– It’s efficient. You’ve already paid for it.

• Read and annotate lecture handouts.• Consult Biochemistry textbook

& work chapter problems.– Most illustrations I use are from Biochemistry “Stryer5e”

by Berg, Tymoczko, & Stryer (Ch. 1-3)Published by W. H. Freeman, & Co. 2002.

– URL: http://bcs.whfreeman.com/biochem5/• Consult the TA or a tutor as you go along, even if you’ve

never needed help in school before.

“I thought I could catch up later.”

How to study Biochemistry

7

1. pH (acid vs. base), buffers2. equilibrium constant, rate constant3. resonance structures4. oxidation/reduction5. proteins, nucleic acids, carbohydrates & lipids6. cell organelles and walls7. and many others -

But, please ask if a term seems to comeout of the blue!

What do you need to know already?(i.e. are these familiar?)

8

Optional Chemistry Review SessionsMonday was Basic Chem. - Prof. SheaLater in Semester - Organic Chem. -

Prof. Rubenstein

Would you like to go for

Honors in Biochemistry? Please fill out card in 4-403 BSB

Biochemistry Dept. Office

© You are welcome to shareyour notes but not to profit from sharing your copy with anyone.

Please Expect Daily HandoutsPosted Online &

Leftover Copies >> 4-403 BSB

Announcements

Exam #1See Course Syllabus

Study Guide (Sample ?’s)available

9

http://www.shol.com/agita/pigs.htm; http://www.shol.com/agita/wolfside.htmPLEASURE PRINCIPLE VERSUS REALITY PRINCIPLE From: The Uses of Enchantment, The Meaning and

Importance of Fairy Talesm by Bruno Bettelheim, Vintage Books, NY, 1975http://www.shol.com/agita/pigpsych.htm

Once upon a time there were 3 little pigs.The time came for them to leave home and seektheir fortunes. Before they left home, theirmother told them,

" Whatever you do, do it the best that you canbecause that's the way to get along in the world.”

Biochemistry: The Big Bad Wolf?

Bottom line:Build a brick house to prepare for the future, yourother classes, the Boards, and your patients.

If this is “Easy Street” for you - reach ou and helpa classmate who’s seeing this for the first time.

10

• Complexity vs. Simplicity– Complex molecules made from simple

components.• Hint: This makes it worth learning the vocabulary early.

• Balance.– Energy is conserved. Mass is conserved.

• Follow the money/carbon/phosphate.• No explosions, no pressure-cookers.

– Reactions @ 1 atm, 37 ˚C need energy andcoordination.

• A place for everything.– A cell is a parallel processor & labyrinth.

• Water, water everywhere.– Water as a reagent, solvent, heat reservoir, etc.

Common Themes of Biochemistry

11

We are hereThese guys withstood mass extinctions using

proteins & DNA like ours.

Nematode (worm)development - lineage ofevery cell now known –they fit under amicroscope & we don’t

We Gain Knowledge & UnderstandingAcross Eons & Species

Cancer's Break-in Tools Possibly Identified:Nematode Worm Provides Model Of Invasive Cancer

12http://www.sciencedaily.com/releases/2009/08/090817142735.htm

13

Common Ionization ReactionsDepend on pH

Lehninger 4e, Ch. 2

14

Better Living Through Chemistry

Lehninger 4e, Ch. 2

15

Buffer (A-, HA) = small pH Change

Lehninger 4e, Ch. 2

16

• building blocks of proteins &precursors for– hormones,– neurotransmitters– and nucleic acids

• polyprotic acids/bases• functional molecules in and of themselves• mainstream collection of 20

– metabolism will be presented later– some are “essential” -

• must be eaten in diet

“Tell them they have to know all 20

of them cold!”Prof. Rubenstein

Amino Acids

COO -

C

H

HH3N+

Glycine

•http://www.biology.arizona.edu/biochemistry/problem_sets/aa/aa.html

17

Advice: Memorize abbreviations and structures shownin attached study guide for 20 common amino acids.Try self-paced quizzes at

http://www.biology.arizona.edu/biochemistry/problem_sets/aa/AAid/ID.html

http://www.biology.arizona.edu/biochemistry/problem_sets/aa/AAcodes/codes.html

IUPAC names exist for amino acids, but mostly they arereferred to by their common names.

Abbreviations for Amino Acids

18

(Non) Essential Amino Acids10 Non-Essential Amino Acids

Humans can synthesize1. alanine A2. asparagine N3. aspartic acid D4. cysteine C5. glutamic acid E6. glutamine Q7. glycine G8. proline P9. serine S10. tyrosine Y

10 Essential Amino AcidsMust obtain from diet1. arginine R2. histidine H3. isoleucine I4. leucine L5. lysine K6. methionine M7. phenylalanineF8. threonine T9. tryptophan W10. valine V

DANCE Q GYPSY MILK THRF VW

19

Size range from proton (glycine) tolarge ring structures (tryptophan)

ChargeMay be neutral, positive, negative at pH of bloodOnes with neutral sidechains are zwitterions(see next slide)

H-bonding Capacity many and varied

Chemical Reactivity hydroxyl, sulfhydryl, amino, carboxyl groups

Spectral Properties a few have strong UV signals

All At pH 7: NH3+ (pKa of ~8) & COO-(pKa of ~2)

pKa = pH where [R-]=[HR] (Ka=[H+][A-]/[HA])

Fundamental Properties of Amino AcidsSide Chains Reveal Functionality

Graphics of side-chains may be found at the Arizona Biochemistry website. Gly vs. Leu is at http://www.biology.arizona.edu/biochemistry/problem_sets/aa/Anim/Gly_Leu.html

20

Zwitterions & Side Chains• Indvidual amino acids that have uncharged side chains arezwitterions in solution at neutral pH because the amino group isprotonated (positive charge) and the carboxyl group is deprotonated(negative charge), but electrically neutral (net charge is zero).• In solution, the nature of the amino acid R-groups (side chains)make the greatest contribution to structure-function relationships ofpeptides and proteins.

• In aqueous proteins (ones located in water), hydrophobic(water fearing) amino acids will more frequently be found in theinterior, shielded from direct contact with water.The reverse is the case for membrane proteins (ones embeddedin lipids).• Conversely, the hydrophilic (water loving) amino acids aremore frequently found on the exterior of aqueous proteins as wellas in the active centers of enzymatically active proteins

21

+,0 +- 0,-

Titration of Amino & Carboxyl Groupof Free Amino Acid with Uncharged Sidechain

22

Legend: Titration

+1 @ low pH (below 2) = high [H+]COOH = 0 (pK 2-3), NH3

+ = 1mixed @ pH = ~2 the pK of the (COOH) group

0 @ pH = pI = 1/2 {pK (COOH) + pK (NH3+)}

Isoelectric zwitterioncarboxyl group COO- , amino group NH3

+

mixed @ pH = ~9, the pK (NH3+)

-1 @ high pH = low [H+] NH3

+ loses a proton (pK ~8-9, NH3+ k NH2)

23

Titration of Alanine (R=CH3)

COO -

C

CH3

HH3N+

Neutral Amino Acid (R is neutral)

R = CH3 moles of OH- added per mole amino acid

pH

0

14

2.34

6.02

9.69

0 1 2moles of OH- added per mole of Alanine

NH2NH3

+

COOHCOO-

http://cti.itc.virginia.edu/~cmg/Demo/titr.html

(Lippincott)

24

Legend: Titration of AlanineThe COOH and NH2 groups are capable of ionizingIonic equilibrium reactions can be written as follows:

R-COOH R-COO- + H+

R-NH3+ R-NH2 + H+

In acid solution, both the amino group (-NH3+) and the

carboxyl group (-COOH) are protonated.As the pH rises ([H+] drops), the carboxyl group is the first to

release a proton around pH 2-3 (pKa = 2.34). The dipolarform persists until the pH approaches 9 - 10 (pKa = 9.69),when the protonated amino group loses a proton.

For HA <--> H+ + A-, Ka =[H+][A-]/[HA] = acid dssn. constantHenderson-Hasselbalch Eq: pH = pKa + log{[A-]/[HA]} p Ka = pH where [A-] = [HA]

25

Adenosine TriphosphateA. Space fillingB. Ball-and-stickC. Skeletal(Drawings from Stryer)

Standard Color CodeCarbon: Black/grayOxygen: RedNitrogen: blueHydrogen: white/smallSulfur: yellowPhosphorus: purple

A. B. C.

Alternate Representations of ATP

26

Legend

Space filling: These models are constructed by drawingeach atom as a van der Waals sphere with the atom’s nucleusat the center of the sphere. They are useful because theyshow how much space an atom (or molecule) occupies.

Ball-and-stick: The ball and stick model is not as realisticas space-filling models because the atoms are depicted asspheres of radius smaller than the van der Waals radius.However, the bonding arrangement is easier to see. Morecomplex structures can be view with the ball-and-stick model.

Skeletal: The skeletal model is the simplest model andshows only the molecular framework. The skeletal models areused to show large molecules such as proteins with severalthousand atoms.

27But this would be painful synthesis method for humans!

Pre-biotic Synthesis of Amino AcidsGlycine, Alanine, Leucine, Glutamic Acid

28

LegendIn 1953, Stanley Miller subjected a mixture of methane, ammonia,

hydrogen and water in a 3-part system (gas, vapor, liquid) to theaction of an electric discharge. Oparin and Haldane had alreadypredicted the results of this: A multitude of organic molecules,sugars and amino acids were formed. These reactions were moreefficient if the system was held at a higher temperature. Theorganic material was found mostly in the water chamber. The vastmajority of organic molecules are not stable in an oxidizingatmosphere - such as the one we now have.

All amino acids have a similar structure: central alpha carbon amine group carboxyl group hydrogen

Only difference is the ‘R’ group

29

LMNOP Mnemonic: L-aMino acids iN Our Proteins

Hands-on approach - make isomers in your kitchen using EdibleMolecular Models: gumdrops/marshmallows & toothpicks

Human Amino Acids are L-isomersMirror images are D-isomers

30

LegendBecause the alpha carbon is asymmetric, each amino acid can

exist as two enantiomers. The exception being Glycinewhose ‘R’ group is a hydrogen.

D-amino acids can be found in nature, but only the L-isomersare used to form proteins.

D-isomers are most often found attached to the cell walls ofbacteria and in antibiotics that attack bacteria. The presenceof these D isomers protects the bacteria from enzymes thehost organism uses to protect itself from bacterial infection byhydrolyzing the proteins in the bacterial cell wall.*

If they look like the same molecule to you, try building themusing whatever resources are available (gumdrops &toothpicks).

http://www.the-scientist.com/blog/print/55983/

http://www.the-scientist.com/blog/print/55983/

31Scanning electron microscope image of Vibrio choleraeImage: Wikipedia Commons

33

R R

Amino-Carboxyl- Cα

Simplest Amino Acids: Glycine & AlanineR(side chain) = Hydrogen or Methyl Group

34

Legend: Glycine and Alanine

Glycine• Simplest amino acid with a hydrogen as its side chain• It’s the only amino acid which is achiral.• Optically inactive• Of all the amino acids formed in Miller’s pre-biotic soup

experiment, Glycine was the most abundant• Nonessential amino acid manufactured in the liver

Alanine• L-Alanine is one of the most important amino acids

released by muscle. Excess L-Alanine may be broken downinto glucose and used as an energy source.

• Alanine is also an inhibitory or calming neurotransmitter inbrain

• Nonessential amino acid made from pyruvate

35

• Stereochemistry:– Dashed bonds go back “behind” paper/screen.– Pointed bonds come out in front.

Glycine & Alanine Stereochemistry

36

R (side chain) = Proton and Methyl Group

Glycine & Alanine Fischer Projections

37

• For all of these, R (side chain) is– neutral, increasingly long or branched– favorable for interior hydrophobic core of proteins

• Note: Sulfur in Methionine

Other Aliphatic Amino Acids:Valine, Leucine, Isoleucine, Methionine

38

Legend: Aliphatic Groups• Aliphatic: implies that the protein side chain contains only

carbon or hydrogen atoms. However, it is convenient toconsider Methionine in this category. Although its side-chain contains a sulfur atom, it is largely non-reactive,meaning that Methionine effectively substitutes well withthe true aliphatic amino acids.

• Aliphatic groups are also hydrophobic (would prefer toself-associate rather than interact with polar watermolecules). Increasing bulk and length shown below.

39

• Proline– is the only amino acid without a free amino group– serves as an elbow joint or helix kinker in proteins

Carboxyl-

Proline - a kinky imino acid

40

Legend: ProlineException to the general structure of an

amino acid: contains no aminogroup, therefore called an ‘imino’ acid(or secondary amino).

A non-essential amino acid that issynthesized from glutamic acid.It is an essential component ofcollagen and is important for properfunctioning of joints and tendons.

In protein, it has a special bondingstructure as an imino acid. Becauseit does not form hydrogen bonds, itmakes an important contribution tothe high-order structure of protein.

Proline can act as a structural disruptorfor alpha helices, and as a turningpoint in beta sheets.

Multiple prolines in a row can create apoly-proline helix.

41

1 ring 1 ring 2 fused rings

Phenylalanine, Tyrosine, Tryptophan“Aromatic” amino acids

42

Legend: Aromatics• Phe: 6-membered ring, hydrophobic• Tyr: hydroxyl group• Trp: Nitrogen in 5-membered ring

• A side chain is aromatic when it contains an aromatic ringsystem. The strict definition has to do with the number ofelectrons contained within the ring. Generally, aromaticring systems are planar, and electrons are shared over thewhole ring structure.

• The aromatic R-groups in amino acids absorb ultravioletlight with an absorbance maximum in the range of 280 nm.The ability of proteins to absorb ultraviolet light ispredominantly due to the presence of tryptophan, whichstrongly absorbs UV light.

43

Strong Ultraviolet (UV) Absorbancefor Tyrosine† and Tryptophan*

Precursors to:† hormones thyroxin,melanin, epinephrine,* neurotransmitter serotonin -“milk/turkey before bedtime”

44

Legend: UV AbsorbanceDetermination of protein concentration by

ultraviolet light absorption (260 to 280 nm)depends on the presence of aromatic aminoacids. Tyrosine and tryptophan have max.absorbance at approximately 280 nm.

Higher order protein structure (hydrogen bonding,and hydrophobic environment) affects UVspectra by modifying the molar absorptivities ofaromatic amino acids. Thus, UV detection ishighly sensitive to pH and ionic strength atwhich measurement is taken.

Many other cellular components, and particularlynucleic acids, also absorb UV light. The realadvantages of this method of determiningprotein concentration are that the sample is notdestroyed and that the measurement is veryrapid.

Although different proteins have different aminoacid compositions and thus different molarabsorptivities, this method can be very accuratewhen comparing different solutions of the sameprotein.

Fig. 1.6, Lippincott

45Amino-

Carboxyl-

Polar Serine & Threonine:like Ala & Val plus Hydroxyl

46

Serine & Threonine:Fischer Projections

Serine can be thought of as a hydroxylated version of alanine and threonine as ahydroxylated version of valine. The hydroxyl groups on serine and threoninemake them more hydrophilic (water-loving) and more reactive than alanine andvaline. Threonine like isoleucine, contains two centers of asymmetry.

47

S

Polar Cysteine - a Staple amino acidLike Serine, but with SH vs. OH

48

Legend: Cysteine• Cysteine is the only amino acid whose “R” covalently

stitches a protein together (using S-S disulfide bonds).• SH group is highly reactive for protein modification.• Cysteine is required for skin, as well as detoxification of

cells. It is found in beta-keratin, the main protein in nails,skin as well as hair. It not only is important in collagenproduction but also assists in skin elasticity and texture.

• Cysteine is also required in the manufacture of the aminoacid taurine and is a component of the antioxidantglutathione. It is useful to detoxify the body from harmfultoxins and help protect the brain and liver from damagefrom alcohol, drugs etc.

49

Cys-Cys Disulfide Bond

50

Legend: Disulfide Bonds

• The formation of "Cystine" can take placebetween 2 polypeptide chains to make across-link between them. This is actuallyan enzyme catalyzed reaction which takesplace in the lumen of ER in cells whenproteins are being exported from the cell.An example is the production ofantibodies by cells in the immuneresponse - antibody proteins containmany Cys-Cys or disulfide bonds.

51

Basic* Amino Acids: Lysine, Arginine, Histidine

*Basic = alkaline, has + charge at neutral pH as a result of the dissociation of theamino group in their side chains. The basic amino acids are strongly polar andnormally found on the exterior of proteins, where they are hydrated.

5212.510.8 6.0

pKa HIGH for Lys, Arg

Caution:pKa values

are perturbedby proteins

Ionizable Side Chains - Basic

53

Acidic Side Chains & Neutral Cousins

54

Legend: Asp/n, Glu/nAsp & Glu: Long side chains that have - charge at neutral pHAsn & Gln: Long side chains that are neutral.

Since an amino acid has both an amine and acid group which havebeen neutralized in the zwitterion, the amino acid is neutral unlessthere is an extra acid or base on the side chain. If neither ispresent then then the whole amino acid is neutral. Amino acidswith an amide on the side chain do not produce basic solutions.You need to look at the functional groups carefully because anamide starts out looking like an amine, but has the carbon doublebond oxygen which changes the property. Amides are not basic.

If the side chain contains an acid functional group, the whole aminoacid produces an acidic solution. The amino acid structurecontains two acid groups and one amine group, which meansthere is a net acid producing effect.

55

4.14.1

Same caution applies:Protein environment canmodify the observed pKa

value.

Ionizable Acidic Side Chains

56

3.1

4.1

6.0

8.3

10.9

10.8

12.5

8.0

VeryVariable

pKa Value for Ionizable Side Chains

57

Uncommon Amino Acids &Post-Translational Modification of Proteins

Hydroxyproline: stabilizes fibers of collagenγ-Carboxyglutamate: needed in Prothrombin, a clotting proteinCarbohydrate-Asparagine Adduct:

often found on secreted proteinsPhospho-serine (phospho-threonine & phospho-tyrosine):Phosphorylation is a very common reversible covalentmodification that is often used as a regulatory “switching” tag

58

Post-Translational Modifications

59

Phosphorylation

60

Catalyze reactions - accelerate to work at body temperatureAll enzymes are gobbledy-ase. polymerase, gyrase; many globular; importantfor cascade processes (not used up in the rxn); integrate “input” from manysources by binding of substrates effectors.

Motility - muscle contractionProteins intertwined in large assemblies, respond to ∆'s in calcium or magnesium,triggered to make length changes on macroscopic level.

Ligand storage and delivery - myoglobin and hemoglobinAnalogy of bank drive-up, to protect the ligand from sticking to the walls, and toprotect the neighborhood from the ligand

Antibodies and other immune system elementsproteins sensors of self vs. non-self; trainable tethers in diagnostic tests

Receptors - for hormones, other chemicalsproteins associated with a barrier; serve as gatekeepers or sentinels.

Support and Protection - skin, bone, hairHigh tensile strength, ability to withstand the weather.

Amino Acid Polymers =Polypeptides or Proteins

61

Critical propertiesPlanar and Rigid

partial double-bondcharacter

Fixed Lengthallows for regular pipe(alpha helix) and barrel (betasheet) structures stabilizedby network of hydrogenbonds.

How are proteins made?Amino Acids are linked by Peptide Bonds

62

1 2 3 Tyr Gly Gly Phe Leu

Synthesis of Peptides/Proteins:from Amino- to Carboxyl- End (“N” to “C”)

Numbering usually starts at amino-terminal residue. When sequences of same protein frommany organisms are being compared, sometimes pseudo-numbering is used, with reference toa single organism (that’s how “negative” amino acid numbers arise

63

C-C, C-N BackboneBond lengths = ~ 1.5Å

Geometry of Peptide Chains

64

Primary Structure of Bovine Insulin:2 Chains Held Together by S-S Bonds

Insulin is a hormone secreted by the pancreas and critical for glucose metabolism.Diabetes therapy often includes insulin supplementation. Insulin was the first proteinto be sequenced (1953, Sanger) - meaning the identity AND order was determined.

65

GlutathioneGlu-Cys-Gly - the oxidized dimeric form has disulfide (-S-S-) bondbetween Cys residues; scavenger for oxidizing agents.

EnkephalinsPentapeptides are “natural opiates” of the brain - responsible forrunner’s high. YGGFL (Tyr-Gly-Gly-Phe-Leu) and YGGFM (Tyr-Gly-Gly-Phe-Met).

AspartameL-Asp-L-Phe-methyl ester is of considerable commercial importancebecause of its use as a sweetener that is not broken down as acarbohydrate would be. The D-form of this is bitter rather thansweet.

Cyclic Peptides: Vasopressin, OxytocinHave -S-S- bond;vasopressin is involved in control of blood pressure;oxytocin induces labor - a positive feedback response

Many Peptides of Physiological Importance

66

Antigen may be peptide fragment of“true”/larger target protein

67

• Primary Structure– amino acid sequence

(ultimately determines3-D structure)

• Secondary Structure– alpha helices, beta

sheets, turns and loops• Tertiary Structure

– protein “folds”including beta barrels,coiled coils

• Quaternary Structure– assembly of multiple

subunits

Levels of Protein Structure

99:163 Instructor: Shea

Filename: 99.163 20 common amino acids

20 "Common Amino Acids" at pH 7 (Although Proline is an Imino Acid, it is conventionally included in this set).

Glycine, Gly, G

COO -

C

H

HH3N+

The pKa values given here are for the R-group of each of the 7 annotated amino acids per Table 3.2 in Biochemistry text by Campbell. Note that these values are slightly different from those in Stryer5e. Don’t memorize to the tenths place! Know the approximate values. Chart shows how charged groups will be in their predominant form at pH 7.

Amino Acids with non-polar side chains

Alanine Ala, A

Valine Val, V

Leucine Leu,L

Isoleucine Ile, I

Proline Pro, P

Phenylalanine Phe, F

Tryptophan Trp, W

Methionine Met, M

COO -

C

CH3

HH3N+

COO -

C

C

H

HH3N+

CH3CH3

COO-

C HH3N+

CH2

C

H CH3H3C

COO -

C

C

H

CH2

H3N+

H

CH3

H3C

COO -

C HN

H2C

CH2

CH2

H2+

COO -

C

CH2

HH3N+

COO -

C

CH2

HH3N+

C

CH

NH

COO -

C

CH2

H

CH2

S

H3N+

CH3

Amino Acids with neutral, polar side chains Serine Ser, S

Threonine Thr, T

Tyrosine Tyr, Y

Cysteine Cys, C

Asparagine Asn, N

Glutamine Gln, Q

COO -

C

CH2

HH3N+

OH

COO -

C

C

H

CH3

H3N+

OHH

COO -

C

CH2

HH3N+

OH pKA = 10.07

COO -

C

CH2

HH3N+

SH pKA = 8.33

COO -

C

CH2

HH3N+

C

O NH2

COO -

C

CH2

H

CH

C

O NH2

H3N+

2

Amino Acids with "carboxyl group" Amino Acids with basic side chains

Aspartate Asp, D

Glutamate Glu, E

Lysine Lys, K

Arginine Arg, R

Histidine His, H

COO -

C HH3N+

CH2

COO - pKA = 3.86

COO -

C

CH2

H

CH2

COO -

H3N+

pKA = 4.25

COO -

C

CH2

H

CH2

CH

H3N+

CH

NH3+

2

2

pKA = 10.53

COO -

C

CH2

CH2

HH3N+

CH2

N

C

NH2H2+N

H

pKA = 12.48

- COO

C HH3N+

CH2

CHC

CH

NHN

H+

pKA = 6.0

(often charged at pH 7 because pK

varies within proteins)

Copyright © 2005 Lippincott Williams & Wilkins

Figure 1.14Key concept map for protein structure.

Side chains of 20 different types

deprotonated (COOÐ) at physiologic pH

On the outside of proteins that function in an aqueous environment, and in the interior of membrane-associated proteins.

in the interior of proteins that functionin an aqueous environment, and on the surface of proteins (such as membrane proteins) that interact with lipids

Weak acids

Release H+

pH = pKa when [HA] = [AÐ]

Buffering occurs ± 1 pH unit of pKa

Buffering capacity

Maximal buffer when pH = pKa

protonated (NH3+ )

at physiologic pH

described by

composed of

and act asis is

are onlyOptically activeD and L forms

L-Amino acids are found in proteins

In proteins most α-COOÐ and α-NH3

+ of amino acids are combined in peptide bonds.

Therefore, thesegroups are not available forchemical reaction.

Thus, the chemical nature of the side chain determines the role that the amino acid plays in a protein,particularly . . .

. . . how theprotein foldsinto its nativeconformation.

Nonpolar side chains

AlanineGlycineIsoleucineLeucineMethioninePhenylalanineProlineTryptophanValine

Uncharged polar side chains

AsparagineCysteineGlutamineSerineThreonineTyrosine

Henderson-Hasselbalch equation:pH = pKa + log AÐ

HA

Amino acids(fully protonated)

Side chain dissociatesto ÐCOOÐat physiologic pH

Side chain is pro-tonated, and generally has a positive chargeat physiologic pH

characterized by characterized by

found found found found

predicts

predicts

predicts

predicts

are composed of can

Acidic side chains

Aspartic acidGlutamic acid

Basic side chains

ArginineHistidineLysine

α-Carboxyl group(–COOH)

α- Amino group(–NH3+)

THE POST-TRANSLATIONAL MODIFICATION CODE

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T O L L F R E E : 1 . 8 8 8 . S E L . P A B S W W W . A B G E N T. C O M

SUMOYLATION UBIQUITINATION PHOSPHORYLATIONMETHYLATION &ACETYLATION

OTHER PROTEINMODIFICATION

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Common Abbreviations in Biochemistry (from Stryer5e)

A adenine HGPRT hypoxanthine-guanine ACP acyl carrier protein phosphoribosyl-transferaseADP adenosine diphosphate His histidine

Ala alanine Hyp hydroxyprolineAMP adenosine monophosphate IgG immunoglobulin G

cAMP cyclic AMP Iie isoleucineArg arginine IP3 inositol 1,4,5,-trisphosphate Asn asparagine ITP inosine triphosphateAsp aspartate LDL low-density lipoprotein

ATP adenosine triphosphate Leu leucineATPase adenosine triphosphatase Lys lysine

C cytosine Met methionineCDP cytidine diphosphate NAD+ nicotinamide adenine dinucleotide (oxidized form)CMP cytidine monophosphate NADH nicotinamide adenine dinucleotide (reduced form)CoA coenzyme A NADP+ nicotinamide adenine dinucleotide phosphate (oxidized form)CoQ coenzyme Q (ubiquinone) NADPH nicotinamide adenine dinucleotide phosphate (reduced form) CTP cytidine triphosphate PFK phosphofructokinase

cAMP adenosine 3',5' -cyclic monophosphate Phe phenylalaninecGMP guanosine 3',5'-cyclic monophosphate Pi inorganic orthophosphate

Cys cysteine PLP pyridoxal phosphateCyt cytochrome PPi inorganic pyrophosphate

d 2'-deoxyribo- Pro prolineDNA deoxyribonucleic acid PRPP 5-phosphoribosyl-1-pyrophosphate

cDNA complementary DNA Q ubizuinone (or plastoquinone) DNase deoxyribonuclease QH2 ubiquinol (or plastoquinol) EcoRI EcoRI restriction endonuclease RNA ribonucleic acid

EF elongation factor mRNA messenger RNAFAD flavin adenine dinucleotide (oxidized form) rRNA ribosomal RNA

FADH2 flavin adenine dinucleotide (reduced form) scRNA small cytoplasmic RNAfMet formylmethionine snRNA small nuclear RNAFMN flavin mononucleotide (oxidized form) tRNA transfer RNA

FMNH2 flavin mononucleotide (reduced form) RNase ribonucleaseG guanine Ser serine

GDP guanosine dephosphate T thymineGln glutamine Thr threonineGlu glutamate TPP thiamine pyrophosphate Gly glycine Trp tryptophan

GMP guanosine monophosphate TTP thymidine triphosphatecGMP cyclic GMP Tyr tyrosine

GSH reduced glutathione U uracilGSSG oxidized glutathione UDP uridine diphosphate

GTP guanosine triphosphate UDP-galactose uridine diphosphate galactose GTPase guanosine triphosphatase UDP-glucose uridine diphosphate glucose

H Hydrogen UMP uridine monophosphateH2O water UTP uridine triphosphateHb hemoglobin Val valine

HDL high-density lipoprotein VLDL very low density lipoprotein

StryerBiochemAbbrev.xls 99:163, Instructor: Shea