Lecture 1 - building blocks Flashcards
What is the basic structure of amino acids?
pKa - being likely to be protonated or deprotonated
- amino group 9.4 -> likely to accept protons
- carboxyl group 2.2 -> likely to release protons
Do amino acids always have the same orientation?
No. They can have 2 main forms of orientation
- We tend to draw amino acids by starting with alpha C -> than draw amino group in left side while carboxyl on the right
- L-amino acid has H behind itself and R sticking out to the front while in D-amino acids the roles are switched
- If N is left, C is right => L
Where does chirality in natural amino acids from?
Nature usually uses alpha keto substrate that will later become side chain
- Glutamite is attached to a special protein called pyridoxal phosphate (PLP)
2) Amino group of glutamite gets transfered to PLP thanks to the enzymes transaminase (amino donor) alpha-keto-glutarat
3) Now we have a pyridoxamine phosphate (PMP)
4) alpha-keto-substrate in the environment releases water via condensation reaction
5) And attaches to the initial molecule, now forming Ketomine
6) Release of H+ and changes in rotation lead to
7) Quinoidic intermediate
8) Protonation = the step at which chirality is created (there is usually limited space where H+ could be added, more often to the back)- proton is coming from lysine
=> we get the final amino acid
- proton is coming from lysine
What are the 2 classes of amino acids? Give some examples + their function
1) Proteinogenic
- used to build up proteins
2) Non-proteinogenic
- various other functions
NOTE: apart from naturally occuring, we can also chemically synthesis our own (non-natural)
What differentiates essential and non-essential amino acids? Give examples.
Essential AC = groups that need to be consumed in food, cannot be naturally synthesized by our body
Non-essential AC = groups that we produce ourselves
How do we chemically distinguish amino acids?
- Electronically charged side chains
- positive
- negative
- Polar uncharged side chains
- Hydrophobic side chains
- Special cases
How many amino acids do we have?
As of now 23 actually. They added:
- Selenocysteine, Sec, U
- present in seleno proteins in all formas of life
- instead of thiol group it resembles cysteine
- Pyrrolysin, Pyl, O
- in proteins of metabolism of Archae
- N-formylmetheonin,fMet
- initiation of protein synthesis in genes of bacteria and organells (e.g. mitochondria, chloroplasts)
Give 3 letter codes to 1 letter code (we don’t have B, J, X, Z)
Which amino acids are charged?
- Positively charged - take up protons
- BUT histidine tends to be found in environments which shifts its pKa to take up H+
- Negatively charged - release H+
What are amino acids with the polar uncharged side chains?
What amino acids are classified as special case? Why are they called that way?
Special cases - due to variety in their chemical properties, jusr don’t seem to fit anywhere
- Contains the simplest amino acids - glycine
- Proline - side chain is making ring closing towards its own terminus
- Serine similar to cysteine - just different group ending
Which amino acids are considered hydrophobic?
- ring structures -> aromatic -> absorbing UV rays (we can quantify them)
How do 2 amino acids get linked to one another?
Amino acids react by a condensation reaction to form a peptide bond
- carboxyl group binds to the amino group (one has to be flipped around) => side chains are on alternating sides (R1 is in front while R2 back)
Note: starts at the n-terminus -> first side chain -> C prime (carbonyl of formal carboxyl group) -> second amino acid -> side chain -> C-terminal
Draw “EASY” tetra-peptide.
Why are peptide bonds special?
Peptide bonds can twist around itself -> BUT only in certain angles = omega i.e. within the peptide plane (the square)
- calculating the angle between N and alpha carbon = phi, and alpha carbon to prime C = psi
- they also don’t want to clash with bulky side chains -> restricted
What is this called? What does it depict?
We’re looking at the peptide bonds in the picture - with both at 0 degrees, we start at psi 0
-> if we move into positive direction => prefered region creating beta sheet
=> picture shows that proteins do NOT occur at all combinations of psi and phi -> there is only a limited number of prefered locations = Ramachandran plot
- NOTE: we tend to check for it in lab, be wary of axis
What is special in Ramachandran plot of glycine?
- Glycine has less sterical hinderances than others -> has more possible combinations of psi and phi
What is special on Ramachandran plot of proline?
- more limited due to the ring structure -> restrcited flexibility
- rarely found in helix structures because it cannot bend around corners as much
What is meant by amino acid modification in the case of histidine?
Histidine
- In pKa of 6 is actually an uncharged side chain -> BUT if the environment changes it can alter its pKa and become positively charged
-> In that case we have 2 possible forms = Imine-Enamine tautomers
What kind of amino acid modification happens with cysteine?
Under certain conditions an oxidation reaction can happen between 2 cysteine molecules and disulfide bonds can be made => stabilizes secondary structures in place
- happens only outside the cells (reductive environment), cytosolic proteins don’t have these bonds
What other amino acid modification can you think of?
Metall - ions
- molecules that can be bound within protein structures
- e.g. alcohol dehydrogenase
- zink ion held in place by 2 cysteine molecules and one histidine
- during catalysis Zn holds alcohol molecule in position for hydride transfer from alcohol to coenzyme nicotinamide
What is meant by phosphorylation? How does it work (e.g. what drives it, what amino acids would be involved, why is it useful)?
=> side chain hydroxyl groups can form a phospoester bond
- driven by enzymes = kinases
- Phosphate group from ATP gets added to hydroxyl group of Ser, Thr, Tyr (NO glutamic acid or aspartic acid - their OH is negative and doesn’t fit binding of kinase) => negative charge in proteins (two additional electrones), conformation change
- important for cellular signaling
The opposite - dephosporylation
What is the function of ATP? How does its structure look like?
Negative bonds are close together -> breaking them releases energy
- used in biological machinery as a driving force
- ALSO a building block of RNA
Consists of:
- adenine nucleoside base
- five-carbon sugar ribose
- triphosphate group
