BCM 251: Introduction to Proteins - Lecture 2 Study Notes
BCM 251: Introduction to Proteins - Lecture 2: Classification and Properties of Amino Acids
Professor Oleg Reva, Chapters 3.1
Structures and Properties of Amino Acids
All amino acids contain:
One alpha-amino group
One alpha-carboxyl group
Differ in the chemical properties of their side radicals (R-groups)
In proteins, amino acids are linked:
By a covalent bond known as a peptide bond
The term residue signifies the loss of a water molecule (dehydration reaction) during peptide bond formation
Average molecular weight (MW) of amino acid residues = 110 Da
MW of an individual amino acid residue = MW of the amino acid - 18 Da (to account for the water molecule)
Carbon atoms of R-residues are numbered from the carbon attached to the amino and carboxyl groups (a-carbon) using Greek letters (b, g, d, e) or numeric numbering from the carboxyl carbon atom.
Exercises
Exercise 1:
A protein with an MW of 30,900 Da has 2% cysteine residues by weight.
Cys MW = 121 Da
Question: How many cysteine residues does the protein contain?
Amino Acid Classification Based on R-groups
Group One: Nonpolar (Aliphatic) R-groups
Includes the following amino acids:
Glycine (Gly, G)
Alanine (Ala, A)
Leucine (Leu, L)
Isoleucine (Ile, I)
Valine (Val, V)
Proline (Pro, P)
Methionine (Met, M)
Key Points:
Aliphatic refers to the hydro-carbonic nature of the side chains lacking aromatic (benzene) rings.
Hydrophobicity increases with the number of carbon atoms in the hydrocarbon chain.
Generally found inside proteins, except alanine and glycine are ambivalent; they can be located both inside and on the surface of proteins.
Proline
Proline has an aliphatic circular R-group where the terminal carbon is attached to the a-nitrogen.
Ring structure is referred to as an imine group, making proline an imino acid.
Reduces structural flexibility and bands protein chains in proteins.
Methionine
Methionine contains a sulfur atom within its hydrocarbon side chain.
It is hydrophobic and found within the hydrophobic cores of proteins.
Although it has a sulfur atom, it remains chemically inactive with no specific roles beyond helping with protein lipid interactions and stabilizing hydrophobic regions in proteins.
Group Two: Aromatic R-groups
Includes:
Phenylalanine
Tyrosine
Tryptophan
Key Features:
Contain phenyl, hydroxyphenyl, and indole aromatic rings respectively.
Contribute to hydrophobic interactions, ordered by relative hydrophobicity: Phe > Trp > Tyr.
Tyrosine and tryptophan can form hydrogen bonds due to –OH and –NH- groups.
Important for specific protein interactions with DNA and organic compounds.
Function as precursors of various neurotransmitters.
UV Light Absorbance
Tryptophan and tyrosine absorb UV light, leading to characteristic strong absorbance at 280 nm.
This property is useful for detecting proteins in solution, particularly against contamination in DNA/RNA samples at 260 nm (260/280 ratio).
Group Three: Polar Uncharged R-groups
Includes:
Serine (Ser, S)
Threonine (Thr, T)
Cysteine (Cys, C)
Glutamine (Gln, Q)
Asparagine (Asn, N)
Features:
These amino acids are common on the surface of water-soluble proteins.
Serine and threonine have a polar hydroxyl (—OH) group which allows them to form hydrogen bonds with water, enhancing protein hydrophilicity.
Cysteine
Contains a thiol group (—SH)
Can react with another cysteine to form a disulfide bridge (—S—S—), also known as cystine, which is hydrophobic.
Plays a crucial role in stabilizing tertiary protein structures and participates in biochemical reduction reactions controlling cellular redox potential.
Glutamine and Asparagine
Contain amide groups derived from carboxyl groups of glutamic and aspartic acids.
Not ionizable within the pH range of cellular conditions, hence they have no charge.
Act as donors of amino groups in synthesizing various nitrogen-containing molecules.
Capable of forming hydrogen bonds in protein structures.
Can be hydrolyzed back to their precursor acids during post-translational modifications.
Group Four: Positively Charged R-groups
Includes:
Histidine (His, H)
Lysine (Lys, K)
Arginine (Arg, R)
Characterization:
These amino acids have alkaline side chains, positively charged at neutral pH.
Charges arise from an additional amino group in lysine; a guanidine group in arginine; and an imidazole ring in histidine.
Histidine has a pKa ≈ 6.0 making it capable of existing in both protonated and unprotonated states, affecting protein properties and facilitating enzyme activity.
Group Five: Negatively Charged R-groups
Includes:
Glutamic acid (Glu, E)
Aspartic acid (Asp, D)
Features:
Have extra carboxyl groups in their side chains in addition to the alpha-carboxyl.
At neutral pH, these groups deprotonate to form carboxylate anions (glutamate and aspartate), hence they have a negative charge.
Glu and Asp are strongly hydrophilic and participate in interactions with positively charged amino acids and ligands.
Common Proteinogenic Amino Acids
Proteinogenic amino acids:
Amino acids that are incorporated biosynthetically into protein chains by ribosomes.
A total of 20 common proteinogenic amino acids exist, encoded by specific codons in DNA/mRNA.
L-isomers are proteinogenic; D-isomers are not.
Rare or uncommon proteinogenic amino acids resulting from enzymatic modification occur post-translationally.
Uncommon/Rare Proteinogenic Amino Acids
Selenocysteine:
Present in all three domains of life involved in oxidative stress enzymes.
Abbreviated as Sec; encoded by the UGA stop codon plus a Sec insertion sequence in mRNA.
Selenomethionine:
Found in plants responsive to oxidative stress; can affect horses' health.
Abbreviated as Met; encoded by AUG (same as methionine).
Pyrrolysine:
Found in some methanogenic bacteria and archaea, abbreviated as Pyl; encoded by UAG stop codon and requires an additional enzyme for synthesis.
Non-Proteinogenic Amino Acids
Non-proteinogenic amino acids:
Cannot be found within proteins.
D-optical isomers of amino acids are typically non-proteinogenic, but common in bioactive peptides produced by bacteria, fungi, and plants, such as in peptidoglycan.
Notable examples:
b-Alanine: Precursor of vitamin B5 and coenzyme A, also naturally occurs in antioxidant peptides like carnosine and anserine.
Other non-proteinogenic amino acids include ornithine, citrulline, and S-adenosylmethionine (SAM).
Post-Translational Modifications of Amino Acids
Common modifications leading to amino acid derivatives in proteins:
Hydroxyproline and Hydroxylysine: Found in collagen.
Thyroxine: Present in thyroglobulin in thyroid glands.
Phosphorylation: Occurs on Ser, Thr, and Tyr side chains, and on His, Lys, Arg, Asp, and Glu.
Methylation and Acetylation: Seen in histones, contributing to epigenetic regulation of gene transcription.
Glutamate Methylation: Part of bacterial chemotaxis, regulating bacterial movement by methylation of flagella motor enzymes.
Carboxylation of Glutamate: Important in the coagulation cascade.
Desmosine: Synthesized from 4 lysine residues, integral to elastin function in providing tissue elasticity.
Exercises and Questions for Self-Control
Exercise 2: Identify amino acid(s) with given characteristics:
a. Positively charged at neutral pH: Arg, Lys, His
b. Has alcohol or phenolic group: Tyr
c. Contains thiol: Cys
d. Aromatic character: Phe, Tyr, Trp
e. Contains amide group: Asn, Gln
f. Participants in hydrogen bonding: Multiple amino acids including Ser, Thr, Cys, etc.
Exercise 3: List amino acids with specific characteristics:
a. Positively charged at pH 7: Arg, Lys, His
b. Negatively charged at pH 7: Asp, Glu
c. Can form disulfide bonds: Cys
d. Aromatic character: Tyr, Phe, Trp
e. Not chiral: Gly
f. More than one chiral carbons: Thr, Ile, etc.
Questions for Self-Control:
Name at least 4 amino acids that do not occur in proteins: b-Alanine, Ornithine, Citrulline, SAM.
Conclusion
These study notes synthesize the classification and properties of amino acids essential in understanding protein structure and function. The detailed notes can serve as a comprehensive resource for further studies in protein biochemistry.