Biochemistry Part 1

Amino Acids, Proteins, Hemoglobin

What does the R-group represent?

Different amino acids

What is the second C part of?

Alpha Carboxyl group

What is the NH3 called?

Alpha Amino Group

What is the carbon in the middle?

Alpha Carbon

What is physiological pH?

7.4

What is amino group charged at physiological pH?

NH3+

What is the carboxyl group charged at physiological pH?

COO-

List Nonpolar Amino Acids

Glycine, Alanine, Valine, Leucine, Isoleucine, Phenylalanine, Tryptophan, Methionine, Proline

List Polar Amino Acids

Serine, Threonine, Tyrosine, Asparagine, Glutamine, Cytosine

List Acidic Amino Acids

Aspartate, Glutamate

List Basic Amino Acids

Lysine, Arginine, Histidine

Which amino acids in the polar group have side chain hydroxyl groups?

Serine, Threonine, Tyrosine

Which amino acid side chain forms a ring with its own alpha amino?

Proline

Which amino acid has a side chain SH?

Cysteine

Which amino acid is the exception for the alpha-carbon not being a chiral center?

glycine

Which of the following does not belong?

Alanine, Tyrosine, Asparagine, Glutamine

Alanine

What is acidic about glutamic and aspartic acids?

Side chain carboxyl groups donate protons at physiological pH

Enantiomers

non-superimposable mirror image isomers

Base

H+ acceptor (proton acceptor)

Acid

H+ donor, proton donor

Dissociation:

-COOH = …

H+ and COO-

Dissociation:

NH3+ = …

H+ NH2

Conjugate Base

Acids corresponding base after the proton is donated

PKa

pH when there is 50:50 mixture of acid and conjugate based of an ionizable group

Acid = Base

pKa=pH

Low pH means….

high proton concentration

High pH means

low proton concentration

Adding OH in a titration will

reduce H+, increasing the pH

The lower the pKa

the stronger the acid

Amino Acids also

• source of energy

• signal molecules in the nervous system ex. glutamate and glycine

• Precursors for ribonucleotides

Amide Link

reaction between amino and carboxyl group

Amide link also called

peptide bone

How do amino acids join?

dehydration to form a dipeptide

Tripeptide

dehydration of 3 amino aicds

What terminus is located on the left?

N-terminus

What terminus is located on the right?

Carboxyl terminus

Where do peptide bonds form?

between the carboxyl of AA 1 and the amino of AA 2

Draw a tripeptide

Proteins

polymers of amino acids

Most proteins are ____ shaped

globular

Proteins provide

reaction catalysts and solute transport

What is being pointed to at the bottom?

Alpha carbon backbone

What happens in aqueous solution

proteins fold spontaneously into 1 or more compact stable structures

What is associated with the activity of a protein?

folded protein structure

What allows polypeptide chain to fold?

rotation around bonds to the alpha carbons allow chain to bend and fold back on itself

Peptide bond acts

double bond, 6 atoms locked in a plane

Looking at this dipeptide, (N7-C9) what atoms are locked into a single plane by the peptide bond?

Atoms 6-11

Protein Data Bank

depository for proteins structures

What are the 4 levels of protein structure?

Primary, Secondary, Tertiary, Quaternary

Primary Protein Structure

the amino acid sequence

Secondary Protein Structure

regions of localized structure involving the alpha carbon backbone

Tertiary Protein Structure

3-D arrangement of atoms in space

Quaternary Protein Structure

3-D arrangement of subunits in an oligomeric protein

Oligomeric Protein

protein with more than one polypeptide chain

Secondary structure examples

A-helix and B-pleated sheet

What structures the alpha helix and beta pleated sheet

depend on a regular pattern of hydrogen bonding along the alpha carbon backbone between an amide H and a carbonyl O further down the chain or on a parallel

Along the alpha carbon backbone, what bond/functional group would serve as a H-bond donor?

N-H

Along the alpha carbon backbone, what bond/functional group would serve as a H-bond acceptor?

Proteins forming beta-sheets are

fully extended

What bonds form beta-sheets

perpendicular H bonds to the axis of the protein chain

Alpha helix is ___bending of the ______.

maximum, peptide chain

Alpha helix hydrogen bonds

run parallel to the direction of the chain, one amino acid to the another 4 amino acids

Where do the R groups point in the helix

point from the cylinder

What secondary protein structure has fully extended polypeptide chain regions and H-bonds extending perpendicular to the chains?

Beta-sheet

Supersecondary Structures

specific combinations or arrangements of secondary structures found repeatedly in different proteins with related functions

motifs

supersecondary structures

Common supersecondary structures

(b)beta meander, (d)beta barrel, c helix turn helix

Supersecondary structures require

sharp turns in a protein chain allowing helices/ sheets to align side by side in specific combinations

What two amino acids are found at sharp turns in the protein chain? Why?

Glycine (small size allows a turn)

Proline (ring geometry favors a turn)

Domain

parts in a modular design of the largest eukaryotic proteins where each exon codes for a domain in the final protein

Domain gives the protein

ability to bind ATP

What does the tertiary structures include?

side chains, helical and pleated sheet regions, prosthetic groups

Prosthetic Group

tightly bound non-protein cofactor required in a proteins structure/function

Apoprotein

protein with prosthetic group removed

Holoprotein

protein complete with prosthetic group

Types of interactions stabilizing tertiary structures

noncovalent forces: H bonding, electrostatic attrations, hydrophobic interactions

covalent forces: Disulfide bridges

Denaturation

loss of protein structure (2, 3 and 4)

What can denature proteins

organic solvents, detergents, H-bonding agents, temp changes

Detergents, organic solvents, hydrogen bonding agents and high temperature are denaturing agents because

They distrupt some or all non-covalent bonds needed in secondary and tertiary structures

The Anfinsen Experiment studied

The ability of RNAse to refold and regain its function following removal of denaturing agents supports the overall view that primary structure dictates folding and function.

What was the reducing agent in the Anfinsen experiment

RSH

What was the H- acceptor and donor in Anfinsen Experiment

Urea

The removal of RSH and Urea

resulted in the protein regaining its folding position

What happens to most protein in aqueous solutions

fold spontaneously

What is unique about RNAse

doesn’t need help folding correctly

Heat Shock Protein

how bacteria survived a sudden jump in temperature, and synthesized specific proteins that helped prevent other proteins from denaturing irreversibly.

70 hsp, 60 hsp means

bind to the protein as soon as appears from ribosome, prevent from aggregating or folding prematurely and helping it fold afterwards. Most universal

What is a chaperone protein

help prohibit unwanted protein folding, nonpolar

Two chaperone proteins

HSP 60 and HSP 70

What diseases are associated with mid-folding proteins?

alzheimers and parkinsons

Misfolded proteins can

aggregate and result in cell death

Three types of protein folding

Cooperative formation of all native interactions, collapse into a molten globule, fomation of first folding domain

Natively unfolded proteins

only primary structure, usually proteins that bind to something. Must be unfolded to bind

For a protein to be ‘intrinsically unstructured’ or ‘natively unfolded’, what would you predict must be missing?

Significant # of non-polar amino acids

Majority of proteins and enzymes are

globular, apple-like

Ligand

small molecule binding a specific site on a protein

Examples of a globular protein

myoglobin

Myglobin is a

hemoprotein

Heme is

prosthetic group of hemoprotein

Hemoprotein function in oxygen binding so

oxygen is its ligand