Lecture 3 Flashcards
Big picture items
- There are 20 different amino acids
- Each amino acid has a common “backbone” but a different “side chain”
- The properties of the side chains span a wide range
- Modified amino acids play important functions
- Modification of amino acids in proteins is critical to life
- Amino acids can be linked together by peptide bonds
- Several oligopeptides have important cellular functions
- Proteins are synthesized by ribosomes
Amino acid structure
R is the “side chain”
Increasing hydrophobicity of the side chain
ala< lle < phe
A zwitterionic α-amino acid
A zwitterionic α-amino acid
Amino acids with an aliphatic, nonpolar side chain
Not many H-bond acceptors or donors in the side chain of all these amino acids. Only the S in the Met is a rather poor H-bond acceptor.
gly, ala, pro, val, leu, iso, meth
Proline is unique
Its side chain makes a ring by bonding with its main chain nitrogen.
Glycine is also unique
has no side chain.
Isoleucine
is one of only two amino acids with a chiral side chain
Amino acids with an uncharged, polar side chain
Plenty of H-bond acceptors and donors in the side chains of all these amino acids!
ser, thre, cyst. asparagine (asn), glutamine (gln)
Cysteine is quite special
- The pK of its SH is ~ 8.3
- S– is a good nucleophile
- It is good in coordinating metals
- Can form disulfide bridges
Amino acids with a positively charged side chain
lys, arg, hist
Histidine (His) is very special:
- Its pK of ~ 6 means that at neutral pH the imidazole ring is both in its protonated and unprotonated state; at a pH below the pK a larger fraction is protonated than unprotonated; at pH values above the pK a larger fraction of the side chain is unprotonated than protonated.
- It is often involved in acid-base catalysis
- The side chain is good in coordinating metals
Amino acids with a negatively charged side chain
aspartate (asp), glutamate (glu)
• These side chains are very hydrophilic.
• The side chain carboxylates occur often in active sites
• The carboxylates can coordinate metals – in particular, Mg2+ and Ca2+ love them.
Amino acids with an aromatic side chain
phen, tyr, trypt
Which two of these side chains could you call “amphiphilic”?
The aromatic side chains of amino acids
absorb UV light
Phe absorbs at 258 nm – but is not shown because it absorbs much less than Tyr> and Trp.
Below and above the pKa….
NOTE: The pKa of the same functional group can be different in different molecules.
• the pK of the side chain amino group of a Lys is different from that of the α-amino group of the N-terminus of a protein.
• the pK of the OH of a Ser side chain is so high that we do not consider it for this class, but the pK of the OH of a Tyr side chain is lower (and you have to know it).
Biologically active amino acid derivatives
These are not incorporated into polypeptide chains of proteins
gaba, histamine, dopamine, thyroxine
Biologically active amino acids play crucial roles in cell-to-cell communication.
E. g. the top three are neurotransmitters, and thyroxine is a hormone
Dopamine and the Synapse
Dopamine is an important neurotransmitter (among many others)
Neurotransmitters are compounds which travel across the “synaptic cleft” between two neurons
More precisely: from the axon of the presynaptic neuron to the dendrite of the postsynaptic neuron
Dopamine and Parkinson’s Disease
Dopamine is synthesized in two enzymatic steps from the amino acid tyrosine, via 3,4-dihydroxyphenylalanine (also called “L-DOPA”)
Deficiencies in the dopamine production in the brain is correlated with “Parkinson’s disease”, which often starts with relatively mild tremors, but usually has many other effects including speech and motion disorders, and can progress to a truly devastating disease.
Giving Parkinson patients L-DOPA is one of the methods which gives some relief.
Serine phosphorylation and dephosphorylation
Reversible modification of specific amino acids is extremely important in “signal transduction” in biology.
“Protein kinases” attach phosphoryl groups to specific Ser, Thr and Tyr side chains.
“Protein phosphatases” remove these phosphoryl groups
The selective phosphorylation or dephosphorylation of specific proteins allows cells to “sense” the environment, such as reacting to the presence of “insulin”.
Key: after phosphorylation at one or more sites, the properties of the protein differ.
Protein Glycosylation
A very common type of modification of side chains on the protein surface.
One or more sugars are attached to one or more specific residues of a protein
In eukaryotic organisms:
• Almost all secreted and membrane-associated proteins are glycosylated.
• Protein glycosylation is important for many functions.
One of these functions is forming the “extracellular matrix (ECM)” in higher organisms
• The ECM is the mixture of proteins and oligosaccharides between cells
• The ECM is key to positioning cells properly with respect to each other
• The ECM is crucial in very complex processes like:
• Developmental biology
• Wound healing
Protein Glycosylation 2
- Two major types of glycosylation are:
- O-glycosylation
- The oligosaccharide is attached to side chain O of a Ser or Thr
- N-glycosylation
- The oligosaccharide is attached to side chain N of an Asn:
Attaching sugars to a protein occurs during the secretion of a protein
There are often many types of saccharides joined together forming an “antenna”
The process of creating an oligosaccharide antenna is very complex
(For the exam you do need to know the concepts of “core” and “antenna”, but not the names of the different sugars).
Biologically active (oligo)peptides
Aspartame is a dipeptide used as an artificial sweetener
• condensation of L-aspartic acid and (the methyl ester of) L-phenylalanine
• 200 times sweeter than sugar
• binds to the taste receptors TAS1R1 and TAS1R2
In Glutathione: a Glu is linked in an unusual way to a Cys, and the Cys is linked in the standard way to a Gly
Glutathione plays an important role in maintaining the reducing environment in cells.
(NOTE: the Glu-Cys-linkage (red arrows) is via the side(!) chain of the Glu!!)
Condensation of two amino acids forming a peptide bond
The result is a “dipeptide”.
The red bond in the dipeptide is the “peptide bond”.
By repeating this condensation reaction, long “polypeptide chains” are obtained.
In all living organisms this process is carried out by the “ribosome”.
A tetrapeptide
Ala-Tyr-Asp-Gly (three-letter code)
or
AYDG (one-letter code)
(The convention is to write peptide and protein sequences with the N-terminal residue at the left)
The pKa of main chain termini
Although there are of course only two ends per peptide or protein chain,
it is still important to know that:
The pKa of the N-terminal -NH3 + is ~8;
the pKa of the C-terminal -COO- is ~4.
Example: it is the N-terminal amino group of influenza virus haemagglutinin which:
• senses the lower pH in the endosome, and becomes protonated,
• triggering the tremendous conformational change crucial for infection
Protein synthesis is carried out by the ribosome
Characteristics of a bacterial ribosome
• Consists of 66% ribosomal RNA (wires) and 34% proteins (spheres)
• Total molecular weight ~ 2.5 MDa
• Binds message RNA (mRNA) which contains the codons encoding the sequence of amino acids in the polypeptide chain
• Binds a succession tRNA’s (transfer RNA’s) charged with amino acids
• The synthesis of the polypeptide chain is carried out by ribosomal RNA, hence the ribosome is a ”ribozyme”
The ribosomes in eukaryotes are similar but somewhat more complex.
A few major ribosome features
• Two subunits:
• small (yellow – called “30S”)
• large (blue – called “50S”)
• Three tRNA binding sites (magenta, green and gold)
• The growing polypeptide chain exists via a tunnel
