Unit 4 Flashcards
Do electrostatic interactions need to be precisely aligned to get significant binding and is the distance between interacting groups critical for binding?
Distance and precise alignment is very important
Do hydrogen bonds need to be precisely aligned to get significant binding and is the distance between interacting groups critical for binding?
Both are very important. Attraction is the greatest when the 3 atoms are arranged in a straight line
Do van Der Waals forces need to be precisely aligned to get significant binding and is the distance between interacting groups critical for binding?
Distance is important but precision alignment isn’t
Do hydrophobic interactions need to be precisely aligned to get significant binding and is the distance between interacting groups critical for binding?
Distance is important but precise alignment isn’t
Discuss the importance of binding energy in enzyme catalyzed reactions
The interaction between the enzyme and substrate is stabilized by the formation of these noncovalent bonds. Formation of each weak interaction in the ES complex is accompanied by release of a small amount of free energy that stabilizes the interaction. This energy is the binding energy, and it is a major source of free enrgy used by enzymes to lower the activation energy of a reaction so it can be faster.
T or F: Covalent interactions and metal ions don’t contribute to catalysis
False
Describe general acid-base catalysis. What is the general purpose?
Many biochemical reactions occur through the formation of unstable charged intermediates that tend to break down rapidly to their reactant species. Charged intermediates can often be stabilized by the transfer of a proton (by an acid) or the removal of a proton (by a base). The protons are transferred between an enzyme (AA residues) and substrate or intermediate
*Helps enzymatic processes by favoring the production of products
*H-bond donors and acceptors that are not water!
Which amino acid side chains can function as acid-base catalysts?
Glutamate
Aspartate
Lysine
Arginine
Cysteine
Histidine
Serine (IS NOT CONSIDERED IONIZABLE)
Tyrosine
8 in total
*these will function as both acid and base
Describe covalent catalysis. What is the purpose of covalent catalysis?
- In the covalent catalysis, initially, there is a temporary covalent bond formed between the enzyme and substrate
- The presence of a covalent catalyst, an enzyme with a nucleophilic group will bind with the enzyme, breaking the bond between the enzyme and substrate which would give you the same products (just with the nucleophile as a product too)
- This formation and breakdown of a covalent bond intermediate creates a new pathway for the reaction, but catalysis results only when the new pathway has a lower activation energy than the uncatalyzed pathway. Both of the new steps must be faster than the new reaction
- Several amino acid side chains (same as the acid-base catalyzed ones) and some functional groups of enzyme cofactors can serve as the nucleophile
Describe the function of metal ions. Many enzymes require metal ions for activity
- Metals can either be tightly bound to enzymes or taken up from solution along with substrate
- Ionic interactions between the enzyme bound metal and an substrate can help orient the substrate for reaction or stabilize charge reaction transition state (by stabilizing the transition state, you are getting product)
- Metals can also mediate oxidation-reduction reaction sby reversible changes in the metal ion oxidation state
What can metal ions additionally do?
- Metals can also mediate oxidation-reduction reaction sby reversible changes in the metal ion oxidation state
List two reasons why enzyme activity is affected by pH
1) Depending on the side chains can act as either an acid or base in an acid-catalyzed reaction
2) Removing/adding can eliminate ionic interactions between metal ions and substrate
In a folded protein, nearby amino acid side chains can influence pK of a specific side chain. Discuss the effect of a positive microenvironment on the pK of aspartic acid. Will this positive microenvironment have the same affect on the pK of histidine?
1) Aspartic acid can be negative or neutral. In a positive microenvironment, it wants to be negative so it can interact with the positive charges so it does not want to be protonated. When pH>pKa, you are deprotonated. So you want the pKa to decrease so it is more likely that you would have a higher pH value than it and stay deprotonated.
2) It will have the same effect on Histidine. This is because histidine wants to be neutral in a positive environment which means it wants to be deprotonated. That means you want pH>pK so you want your pK to decrease.
Describe the evolution of protein families
- Gene duplications and mutations can create new enzymes
- If a gene, like hexokinase in this example, were duplicated by accident, having two hexokinase genes might be passed down generations.
- Mistakes can occur causing changes/mutation in the duplicated gene
- The altered protein produced from this mutant gene can bind a new substrate which gives the cell a new function (most of this is very rare)
- If no gene duplication comes before the mutation occurs, the original function of teh gene product is lost
Discuss the RNA world scenario
- Prebiotic formation of simple compounds, including nucleotides, from components of Earth’s primitive atmosphere or gases in undersea volcanic vents
- Production of short RNA molecules with random sequences
- Selective replication and duplication catalytic RNA segments - refers to the ability of certain RNA molecules to catalyze their own replication and the replication of other RNA molecules with similar sequences and duplicate their segments to have many copies of themselves
- Synthesis of specific peptides, catalyzed by RNA (the amino acids were already in the environment)
- Increasing role of peptides in RNA replication, coevolution of RNA and protein
- Primitive translation system develops with RNA genome and RNA protein catalysts
- Genomic RNA begins to be copied into DNA
- DNA genome, translated on RNA protein complex (ribosome) with RNA and protein catalysts
- 8 steps
Discuss the evolution of eukaryotes
- The earliest eukaryote, an anaerobe, acquired endosymbiont purple bacteria, which carried with them their capacity for aerobic catabolism.
- Engulfed purple bacteria multiplies
- Overtime, some bacteria genes moved to the nucleus and the bacterial endosymbionts became the mitochondria
- Then, photosynthetic cyanobacteria subsequently became endosymbionts of some aerobic eukaryotes and multiplies. Now the cell can make ATP using energy from sunlight
- Eventually some cyanobacterial genes move to the nucleus, making the chloroplast
Genome
Complete set of genetic material and information in organism or cell
Homolog
When two genes share readily detectable sequence similarities, their sequences are said to be homologs and the proteins tehy encode are homologs
Paralog
If two genes in a family (two homologs) are present in the same species, they are referred to as paralogs
Ortholog
If two genes that share similar sequences are not in the same species it’s considered ortholog
