CHEM  30 B    Dr. R. Rinehart
Chapter 19   PROTEINS

 Proteins are the most important molecules in living organisms, because they are involved in everything that the organism does. They are polymers of amino acids.   The DNA in the cell genome is essentially a set of instructions for the assembly of the thousands of different proteins which the cell needs to function.

PowerPoint-type presentations on amino acids and proteins
by Warren Gallagher at the University of Wisconsin, Eau Claire
http://web.archive.org/web/20060504011433/http://www.chem.uwec.edu/Chem150_S06/Pages/lecture-materials.html
scroll down to > Lecture 6

A really good, well-illustrated chapter on amino acids and proteins
from Biochemistry Online by Henry Jakubowski at
College of Saint Benedict / Saint John's University is available at
http://employees.csbsju.edu/hjakubowski/classes/ch331/bcintro/default.html

A really great text is available online in PDF format
Protein Structure and Function
by Gregory A Petsko and Dagmar Ringe (New Science Press, 2004)
http://www.new-science-press.com/browse/protein/contents
Available now by subscription only

 I. AMINO ACIDS [see the tables for names and  structures and other factoids]

see the Chapter 16 amino acid table
see the chapter 19 alphabetical amino acid table

            A. General structure
                        1. Carboxylic acid with amino group at position #2 [“a” to the -CO2H]
                        2. Fisher projection: all are L- except glycine
                        3. 20 different R-groups or “side chains;”
                                  AA’s can be grouped into four families based on polarity of side chain

                                    a. Nonpolar “hydrophobic”: GLY, ALA, VAL, LEU, ILE, PHE, PRO, MET, TRP
                                    b. Polar, nonionic/ “neutral”: SER, THR, TYR, CYS, ASN, GLN
                                    c. Polar, cationic  (+) [“basic”]: HIS, LYS, ARG
                                    d. Polar, anionic (-)  [“acidic”]: ASP, GLU

Chime introduction to amino acids, by Örjan Hansson at Göteborg University
 http://www.lundberg.gu.se/~orjan/bmstruct/ > Amino Acids
Use Netscape!!!
Chime tutorial on amino acids by Timothy Driscoll, from Worth, publishers of 
Lehninger Principles of Biochemistry, 3/e by Nelson and Cox
 http://www.worthpublishers.com/lehninger3d/lold/index.html  > Protein Architecture > 1. Amino Acids
Use Netscape!!!
Chime stuff on amino acids by Duane W. Sears at UC Santa Barbara
 http://tutor.lscf.ucsb.edu/instdev/sears/biochemistry/ > Amino Acids
A really good amino acid subject outline and Chime structures
by Gordon Rule at Carnegie Mellon University is at
http://web.archive.org/web/20051202165858/stingray.bio.cmu.edu/~web/bc/Lec/Lec04/lec04.html
http://web.archive.org/web/20050827014639/stingray.bio.cmu.edu/~web/bc/Lec/Lec04/lec04.PDF
 http://stingray.bio.cmu.edu/~web/bc/Lec/Lec04/lec04.html 
Notes on amino acid side chains and their properties
by Richard A. Paselk at Humboldt State U
 http://www.humboldt.edu/~rap1/C431.F01/C431Notes/C431n12sep.htm 


            B. Properties
                       
1. ZWITTERIONS at pH 7
           
            2. Charge varies with pH [low pH => more (+) ; high pH => more (-)]
                        3. Side chain charge can also vary with pH
                        4. Each amino acid has a unique “isoelectric point” [pI], or specific pH where it
                                    has NO net charge

to see more on the effect of pH on side-chain ionization, go to The MIT Biology Hypertext at 
http://web.archive.org/web/20060423232532/web.mit.edu/esgbio/www/lm/proteins/pka/pKa.html
  http://web.mit.edu/esgbio/www/lm/proteins/pka/pKa.html

      C. Reactions
                        1. Oxidation of CYS:
disulfide bond formation
           
            2.
Peptide bond formation
: the basis of protein structure; proteins are polyamides

To see more on peptide bond formation, go to The MIT Biology Hypertext at
http://web.archive.org/web/20060427180128/web.mit.edu/esgbio/www/lm/proteins/peptidebond.html
 http://web.mit.edu/esgbio/www/lm/proteins/peptidebond.html
and John Kimball's Biology Pages at 
http://www.ultranet.com/~jkimball/BiologyPages/P/Polypeptides.html#proteins
 

II. PEPTIDES
            A. Contain 2 to 50 amino acids
            B. Biologically active as neurotransmitters, hormones, hormone-releasing factors
            C. Examples

 

III. PROTEINS: contain ~50 to ~10,000 amino acids
            A. Molecular weight ~5000 to 1,000,000
            B. Can act as buffers
            C. FUNCTIONS
                        1. Catalytic: ENZYMES
                       
2. Structural: collagen, keratin
                       
3. Storage/nutrition: zein, gluten, ferritin, casein, ovalbumin
                       
4. Protective: immunoglobulins
                       
5. Regulatory: hormones: insulin, glucagon
                       
6. Communication: neurotransmitters
                       
7. Motion: actin/myosin; tubulin/dynein; flagellin
                       
8. Transport: hemoglobin, transferrin

            D. Classification
                        1. By shape: FIBROUS vs GLOBULAR

Clarke Earley at Kent State University has a Chime display of collagen at
http://www.personal.kent.edu/~cearley/PChem/jmol/collagen.htm
http://www.personal.kent.edu/~cearley/PChem/pchem.htm > Collagen
 In Jmol, not Chime, so should work with any Java-enabled browser
Chime and non-Chime pictures of a few globular proteins by Mark Bishop of MPC are at 
http://www.mpcfaculty.net/mark_bishop/proteins.htm
 


                        2. By composition:  SIMPLE: contain only amino acids
                                    CONJUGATED: contain NONprotein “prosthetic groups”
                            glycoproteins, phosphoproteins, lipoproteins, metalloproteins, hemoproteins, etc.          

E. LEVELS OF  PROTEIN STRUCTURE

see a brief presentation of 1o to 4o structure from the MIT Biology Hypertext at
http://web.archive.org/web/20060408055031/web.mit.edu/esgbio/www/lm/proteins/structure/structure.html
  http://web.mit.edu/esgbio/www/lm/proteins/structure/structure.html
and for more detail, see  additional entries below


                        1. Primary:    peptide backbone with specific sequence of amino acids
                                    backbone has amide bonds at every third atom;
                                    for a peptide/ protein with n amino acids, there are (20)n possible sequences 

2. SECONDARY:     orderly pattern of backbone folding due to H-bonding
                       
a.  alpha- [a]- helix

to see a Chime tutorial on the a-helix by F. Reichsman at U. Mass., go to [use Netscape 4.7x!!] http://www.umass.edu/molvis/freichsman/protarch/page_helix/menu.html 
or see a shorter version at
 
http://www.umass.edu/molvis/freichsman/protarch/shortpage_helix/menu.html 


                        b.  beta  [b] structures:    pleated sheets, ribbons, bends, and barrels

to see a Chime tutorial on the b-sheet by F. Reichsman at U. Mass., go to [use Netscape 4.7x!!]
 http://www.umass.edu/molvis/freichsman/protarch/page_sheet/menu.html 
or see a shorter version at
 
http://www.umass.edu/molvis/freichsman/protarch/shortpage_sheet/menu.html 


                        c.  random coil:  neither a nor b
   

another good introduction to protein secondary structure [may work with IE; if not, use Netscape 4.7x!!]
by William McClure of Carnegie Mellon University is at 
http://www.bio.cmu.edu/Courses/BiochemMols/ProtG/ProtGMain.htm

3. TERTIARY:  specific overall 3-D shape due to further folding
                    caused by side-chain interactions
(listed below) with water and with each other.
                        Of many possible 3-D shapes, only the most stable one is usually found;
                                 it is called the native conformation of the protein.
                        a.  salt bridges:  ionic interactions between  and  side chains
                        b.  hydrogen bonds: for side chains containing –OH, -NH2, CONH2
                 
            c.  hydrophobic interactions:  water avoids contact with nonpolar R,
                                    forcing them to ‘hide’ in the interior; their overall geometry
                                     determines their packing pattern
                        d.  disulfide bridges: form when two CYS –SH groups are close together;
                                    -S-S- “lock” protein chains together at that point   

To see Chime structures of a number of proteins in their native conformations
go to the C4 site [use Netscape 4.7x!!] at Cabrillo College at 
http://c4.cabrillo.edu/projects/viewers/index.html
  and select MacroViewer 800x600. 
In addition to the normal Chime popup menu available by right-clicking the image,
there is a control panel with sliders that will let you adjust bond width [start in wireframe display and try it],
sphere radius, slab depth, ribbon size, and hydrogen bond width.
Using the "Display" selection from the popup menu, you will see additional choices such as Backbone,  Ribbons, Strands, and Cartoons. Try various combinations of these choices with different slider settings to reveal information about protein construction.

4. QUATERNARY:       many proteins require multiple subunits to function;
                 these subunits (single peptide chains already folded into 3o shapes) adhere to each
                 other via the same types of interactions responsible for 3o structure between
                 groups on the outer surface of the 3o units;

            additional types of covalent bonds besides S-S may also be present
                                    (ester, amide, aldimine)   

A Chime tutorial covering all levels of protein structure by Timothy Driscoll  [use Netscape 4.7x!!]
designed to accompany Lehninger's biochemistry text
 is available at 
http://www.worthpublishers.com/lehninger3d/lold/index.html    
Chime stuff on protein structure by Duane W. Sears at UC Santa Barbara  [use Netscape 4.7x!!]
 http://tutor.lscf.ucsb.edu/instdev/sears/biochemistry/
 > Proteins
An extensive discussion of the levels of protein structure by John C. Pérez
of Texas A&M's Natural Toxins Research Center at Kingsville is available at
http://web.archive.org/web/20041212233704/ntri.tamuk.edu/homepage-ntri/lectures/protein/polypeptide.html
 http://ntri.tamuk.edu/homepage-ntri/lectures/protein/polypeptide.html
   
Notes on levels of protein structure by Richard A. Paselk at Humboldt State U
 http://www.humboldt.edu/~rap1/C431.F01/C431Notes/C431n14sep.htm
and
 
http://www.humboldt.edu/~rap1/C431.F01/C431Notes/C431n17sep.htm and
 http://www.humboldt.edu/~rap1/C431.F01/C431Notes/C431n19sep.htm and
 http://www.humboldt.edu/~rap1/C431.F01/C431Notes/C431n21sep.htm

5. what happens at one level determines what happens at the next; ultimately,
                       
            the sequence of amino acids controls everything else; and the genetic
                                    information in DNA determines the sequence.
                                    DNA à 1o  à  2o  à  3o  à  4o  à  function

Chime structure of ferritin from Shelley Gaudia at Lane CC is at   [use Netscape 4.7x!!]
http://web.archive.org/web/20040201024554/staff.lanecc.edu/~gaudia/ferritin.pdb
 http://staff.lanecc.edu/~gaudia/ferritin.pdb 
Fibronectin Chime tutorial from Michael Ward and David Marcey at Kenyon College  [use Netscape 4.7x!!]
 http://biology.kenyon.edu/BMB/Chime/Fibronectin/fibro.htm
Hemoglobin Chime tutorial by Lisa Natzke at Kenyon College [use Netscape 4.7x!!]
 http://biology.kenyon.edu/BMB/Chime/Lisa/HEMEMAST.HTM

F. Reactions of proteins

                        1. Hydrolysis: catalyzed by acid, base, or enzymes

                        2. DENATURATION:  
                             loss of biological function associated with changes in 2o/3o/4o structure
                                  caused by:
                       
            extremes of temperature
                                    extremes of pH
                       
            mechanical agitation
                       
            organic solvents
                       
            detergents
                                    exposure to surfaces
                                    heavy metal ions [Pb2+, Hg+, Hg2+, ….]
                       
            H-bond disruptors [urea, guanidinium chloride]

                       
            reduction of S-S bonds

                            denaturation is USUALLY irreversible  

More tutorials:
Chime introduction to amino acids, peptides, and proteins by Örjan Hansson at Göteborg University
 http://www.lundberg.gu.se/~orjan/bmstruct/ 
Protein structure by Paul Reisberg at Wellesley  [use Netscape 4.7x!!]
 http://www.wellesley.edu/Chemistry/chem227/protstruct/prtnstrc.htm 
Protein structure by Dr. Grotzinger of Carnegie Mellon U  [use Netscape 4.7x!!]
 http://www.bio.cmu.edu/courses/03231/ProtStruc/ProtStruc.htm
Voet, Voet, Pratt: Fundamentals of Biochemistry: Life at the Molecular Level, 2nd Edition
http://bcs.wiley.com/he-bcs/Books?action=resource&bcsId=2261&itemId=0471214957&resourceId=5420
animations and other goodies

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© Ronald W. Rinehart, 2002-2007