1. PROTEIN MODELING CHALLENGE
Study the structure and function of the protein:
ABO Blood typing glycosyltransferases
Utilize primary peer-reviewed literature and molecule of the month article
Use the protein Data Base (PDB.org) to obtain structural information
Construct a 3-D model using a foam toober and the imaging program Jmol.
Write an essay about the protein structure, function and the model your group makes.

3. PLAN OF ACTION PROTEIN BIOCHEMISTRY
11/17-11/25 (4 days)
Protein Structure
Protein Side-Chains
Protein Biochemistry
12/1 – 12/10 (6 days)
Jmol tutorial
Practice using Jmol
Model simulations
Beta-globulin
Zinc fingers
OpCa protein

4. PROTEIN MODELING TEAM Thursday 2/26/15 at SUNY Stony Brook
12/11 – 12/19 (~5 class days)
Research Articles on the protein
Write a draft abstract about the protein – DUE 12/18 & 12/19
1/5 – 1/16 (~10 class days)
Develop a model of the protein in Jmol that highlights important parts
Create a 3-D model using foam toobers
1/19– 1/30 (~10 class days)
Construct Display for model
Write final abstract – DUE 1/30/15
MODELS DUE 2/13/15
Protein Modeling Challenge
Thursday 2/26/15 at SUNY Stony Brook

5. PROTEIN BIOCHEMISTRY 2014/15
Proteins
and
Organic Molecules

6. Water is the Cradle of Life
Why Water?
A) Water has a simple atomic structure
1. Contains oxygen bound to two hydrogens by covalent bonds
B) Water is Polar
1. The greater electronegativity of OXYGEN makes water polar
2. Electronegative atoms attract electrons away from
other atoms – these electronegative atoms are negatively charged
3. Water carries two partial charges due to electronegative oxygen
4. Hydrogens carry slight positive charges; oxygen carries a slight
negative charge

7. C) Polar molecules and hydrogen bonding 1
C) Polar molecules and hydrogen bonding 1. Due to slight charges, weak interactions between atoms form 2. Hydrogen Bonds: weak transient (temporary) attractions between an electronegative atom and hydrogen 3. Cumulative effect of hydrogen bonds is the responsible for the many properties of water.

8. Why is water important to proteins?
Proteins are made in cells which are comprised of 70% water.
Polar nature of water plays a critical role in determining the final folded shape of a protein.
Hydrogen bonding interactions directly determine the final structure of a protein
Proteins fold in their lowest energy state – requires minimal bonding

9. Water Lover? Water Fearer?
Hydrophobic
Any molecule or atom that repels water
Usually non-polar or uncharged
Hydrophilic
Any molecule or atom that attracts water
Usually polar, charged, acid or base
Hydrophobicity and hydrophilicity contribute to the overall protein structure

10. Essential Biological Elements
What elements are essential for life?
Examples of biologically important macromolecules: Sugars
Proteins
Nucleic Acids
Lipids

11. Proteins Polymers comprised of amino acid sequences
The specific order of amino acids in a polypeptide interacts with the environment to determine the overall shape of the protein
Amino acids contain three major reactive components
Carboxyl group
Amino Group
Radical (R) group
The R group of an amino acid can be categorized by chemical properties
hydrophobic, hydrophilic, acidic, basic, or ionic
R group interactions determine the structure and function of that region of the protein.

12. Amino Acid Structure

14. Protein Synthesis
Amino acids are connected by the formation of peptide bonds by dehydration synthesis between the amino and carboxyl groups of adjacent monomers

15. Amino Acids Differences
All proteins are made from 19 different alpha amino acids
Proline is NOT an alpha-amino acid
The R group bonds with the alpha carbon and amino group
Alpha amino acids have a central carbon (the alpha carbon) to which an R-group is attached

16. Build 2 amino acids in your group
Moly Mod Kits
Side chain
Build 2 amino acids in your group

18. What group is circled?
Build amino group: one N 2 H

19. What group is circled?
Build carboxy group: 1 C 2 O; Carbon has double bond with 1 O

20. What is circled?
An amino acid has a central carabon alpha carbon; amino and carboxy attach at alpha C; as far away as possible
Add on H & R

21. Chirality Amino acids are chiral
Different forms of the SAME amino acid
Mirror images of each other
These are known as enantiomers
Molecules are referred to as right-handed or left handed
When you place your hands palm-side down your thumb on your right hand is on the left side of your hand

22. Chirality All amino acids on Earth are the L-Form
All life forms use the L-amino acids
This is evidence of common ancestry
Bacteria can convert L-amino acids into D-amino acids for cell wall synthesis

23. Using Bonds …
Compare your MolyMod to this amino acid picture.

24. How are these things put together?
BONDS!
Are “highways” between 2 atoms.
Bonds allow electron movement.
We are concerned with THREE types of bonds:
Hydrogen
Ionic
Covalent

25. Covalent Bonds Two atoms share electrons All sharing is not equal.
When electrons are not shared equally it is called a polar covalent bond.
When sharing is equal
When electrons are shared equally it is called a nonpolar covalent bond.
Look at MolyMod

26. Hydrogen Bonds In our water molecules …
H’s of one water interact with the O’s of another water.
ADHESION – different molecules hydrogen bond with each other
COHESION – the same molecules hydrogen bond with each other
Transpiration in plants, Capillary Action, surface tension
A weak interaction between slightly charged atoms…BUT many hydrogen bonds together can be very strong – like velcro
Look at grey box of water molecules

27. Ionic Ionic One atom gives another atom their electrons
Also called a salt bridge
Ionic: Look at toober red & blue
Van: no model

30. How do Amino Acids bond to each other?
Dehydration
Synthesis N N

31. How do Amino Acids bond to each other?
Dehydration
Synthesis
The removal of a Hydrogen from one molecule and an “OH” from another molecule.
This results in water as a product and ….
A BOND BETWEEN THE TWO MOLECULES.
MODEL it!

32. How do Amino Acids bond to each other?
Dehydration
Synthesis N N
Where is there an OH group and a Hydrogen close enough to interact?

43. Modeling Proteins with Toobers
HOW DO PROTEINS GET THEIR SPECIFIC SHAPE?
Side chains are modeled as plastic magnets and color coded depending on polarity and charge
Placemats are magnetized-serve as classification scheme.
YOUR TASK:
Set all side chains on their respective spots on the placemat.

44. Three basic principles of chemistry
Hydrophobic amino acid side chains will cluster in the middle-less water interaction. Hydrophilic side chains including charged and polar will be exposed on the outside.
When possible, opposite charges attract to form salt bridges.
Cysteine side chains pair up to form disulfide bonds. ..are they hydrophobic or hydrophilic???
Use the color chart and the magnetic placemat to help you determine side chain interactions

45. Important Terms to Know
General Protein Structure
Domain: A protein domain is a part of protein sequence and structure that can evolve, function, and exist independently of the rest of the protein chain
Motif: specific pattern of folding in a protein that is seen in several types of different proteins; motifs do not indicate similar function – these are common patterns
Lobe: area of a protein with a specific chemical nature
Hydrophobic lobe
Cleft: a specific area of a protein that forms a space between areas that may function as a regulatory site
Face: surface feature of a protein, usually formed by several beta-sheets

46. Back to the drawing board.
Things to remember!
The shape of the protein is pre-determined by the amino acid sequence.
NOT ALL amino acid sequences are functional due to shape issues.
A sequence may result in a terribly shaped protein
Stability is KEY issue in protein folding!

47. HOW WE LOOK AT PROTEINS

48. How protein structure is resolved

49. Common Protein Motifs