Class #4, Molecular Biophysics (Physics 621/321), W.F. Reed
Biochemical overview I: Proteins and Nucleic Acids
Unifying notions of biochemistry
* All proteins are made of 20 main amino acids.
* All nucleic acids are made of 4 nucleotides. Virtually unlimited combinations are possible.
* Adenosine triphosphate (ATP) is a universal source of free energy.
* The Genetic Code is carried by DNA in all organisms (except some viruses), and mediates the accumulation and transmission of biological information.
* All biomolecules and processes are the result of evolution.
* Biochemical processes and structures are defined by very precise compositions, conformations and interactions. Minor changes can have drastic biological effects. e.g. D vs. L chirality. Cellulose vs. carbohydrate.
* Organisms are compartmentalized by membranes that mediate matter and energy exchange with the environment.
* The biological milieu is aqueous.
* Biological molecules are built of light atoms: C, H, O, N, P, S
ions Na+, K+, Ca++, Mg++
some Fe, Co and Mn
Proteins
There are 20 main amino acids:
*zwitterionic at physiological pH (for non-ionizable R)
* only L-configuration exists in proteins
The peptide bond
Protein Functions
* All known enzymes are proteins. Virtually all biochemical reactions are catalyzed by enzymes. Proteins themselves exert feedback control in metabolic integration.
* Transport and storage. Proteins transport many small molecules and ions. e.g. Hemoglobin-oxygen
* Motility, muscle action
cilia, flagella, muscle; actin/myosin
* Structural material
bone, tendon, skin; collagen and elastin
* Immune system
anti-bodies, self-identification
* Generation and transmission of nerve impulses
reception and transmission across synapses
* Control elements of DNA
Gene regulation and expression
* Chaperones
protein folding
Levels of Enzyme Organization
Primary structure:
The sequence of amino acids specifying the enzyme.Secondary Structure:
The regularities of the three dimensional sub-structures.a
-Helix
*
a-helix backbone is the peptide backbone: functional groups stick out.* All the main chain CO and NH groups are H-bonded, staggered by 4 units.
* There is a 1.5Ang. vertical rise and 1000 of turn between successive a.a. 3.6 a.a./turn, or 5.4 Ang/turn
* All
a-helices are right-handed.* Two and more helices can wind together to form fibrous bundles; e.g. keratin in hair, myosin in muscle.
Protein secondary structure, cont'd.
b
-sheets
(From Biochemistry, by L. Stryer, Freeman Pub.)
* Protein backbone is fully extended, all-trans. 3.5 Ang. between adjacent a.a.
* sheets can be parallel or anti-parallel and are between different polypeptide strands
* Protein strands can make sharp reverses in direction via
b
-turns
Levels of Protein Structure
Tertiary structure:
The overall 3-D structure of the protein
(From Biochemistry, by L. Stryer, Freeman Pub.)
Protein folding problem: Predict complete secondary, tertiary and quaternary structure from the primary structure.
Protein chaperones - Molelules that discriminate between slowly-folding and misfolded proteins, aid in correct folding and localize with aggregates to inhibit their formation.
Protein aggregate formation occurs frequently in vitro, is suspected to occur in vivo, and are related to amyloid diseases, such as Alzheimers.
