Download 407_lecture_9

Molecular Biology & Biochemistry 694:407
& 115:511
Protein Structure
Sept. 13th, 2005, Lecture
Special thanks for this lecture goes to Dr.
Gabriel Fenteany, Department of Chemistry,
University of Illinois at Chicago
(www.chem.uic.edu/fenteany/teaching/452),
whose slides I liberally borrowed!
3-D Structure of Myoglobin
QuickTime™ and a TIFF (Uncompressed) decompressor are needed to see this picture.
Importance of Proteins
• Main catalysts in biochemistry: enzymes
(involved in virtually every biochemical
reaction)
• Structural components of cells (both inside
and outside of cells in tissues)
• Regulatory functions (if/when a cell divides,
which genes are expressed, etc.)
• Carrier and transport functions (ions, small
molecules)
Levels of Protein Structure
• Primary Structure - amino acid sequence in a
polypeptide
• Secondary Structure - local spatial
arrangement of a polypeptide’s backbone
atoms without regard to side chain
conformation (e. g., -helices and -sheets)
• Tertiary Structure - three-dimensional
structure of entire polypeptide
• Quaternary Structure - spatial arrangement of
subunits of proteins composed of multiple
polypeptides (protein complexes)
Structure of -amino acids
The 20 Amino Acids Found in Proteins
Stereochemistry of -amino
acids
Stereoisomers of -amino
acids
All amino acids are
chiral except glycine.
All amino acids in
proteins are L-amino
acids.
Properties of Cysteine Side
Chain
pKa = 8.3
SH
CH2
H3N+ C COOH
H
H3N+ C COOCH2
SH
SH
CH2
+
H3N C COOH
oxidation
reduction
SCH2
+
H3N C COOH
H
H3N+ C COOCH2
S
S
CH2
+
H3N C COOH
+
H+
+ 2H+
+ 2e-
Side chains with -SH or
-OH can ionize, making
them more nucleophilic.
Oxidation between pair of
cysteine side chains results
in disulfide bond formation.
Note: in cells, oxidative disulfide formation
normally proceeds via a thiol-disulfide
exchange reaction, with (for example) a
natural tripeptide such as glutathione:
R’-SS-G + R”-SH + G-SH
R’-SH + R”-SH + G-SS-G
R’-SS-R” + 2 G-SH
R’-SH + R”-SS-G + G-SH
G-SS-G = oxidated glutathione
G-SH = reducted glutathione
Absorption of UV Light by
Aromatic Amino Acids
Formation of a Peptide
Planarity of Peptide (Amide)
Bond
Quick Time™a nd a TIFF ( Uncomp res sed) deco mpre ssor are n eede d to s ee this picture .
cis and trans Isomers
QuickTime™ and a TIFF (Uncompressed) decompressor are needed to see this picture.
QuickTime™ and a TIFF (Uncompressed) decompressor are needed to see this picture.
The trans isomer is generally more
stable because of steric crowding
of side chains in cis conformation.
“Peptides”
•
•
•
•
•
•
Short polymers of amino acids
Each unit is called a residue
2 residues - “dipeptide”
3 residues - “tripeptide”
12-20 residues - “oligopeptide”
Many residues - “polypeptide”
Examples of Oligopeptides
N- and C-Termini May Be
Modified in Proteins
Primary Structure of Bovine
Insulin
First protein to be fully sequenced;
Fred Sanger, 1953. For this, he won his first
Nobel Prize (his second was for the Sanger
dideoxy method of DNA sequencing).
Evolution and Conservation of
Protein Sequences
Almost all human genetic diseases involve
the disruption of a protein in the body.
Typically, the harmful phenotype(s) of
disease-causing lesions in a protein gene are
caused by effects on (a) the level of expression of
the protein, (b) the activity of the protein, or (c)
the folding of the protein.
[Note: Some effects may be different in
different tissues for the same mutation! For
example, some alpha-1-antitrypsin mutations
exert harmful effects in the lungs (emphysema)
due to lack of anti-elastase activity, and different
harmful effects in the liver (cirrhosis) due to
folding/sorting problems.]