Untitled Quiz

Chapter 1: The Covalent Structure of Proteins

• The essential covalent structural feature of proteins is the peptide bond linking amino acids.
• Natural proteins typically consist of 100-1000 amino acid residues, but can have fewer or more.
• Proteins are mainly built from 18 common protein L-amino acids.
• Proline is an L-imino acid, and glycine is also incorporated into proteins.
• Rare exceptions include L-selenocysteine.
• D-amino acids aren't typically incorporated biosynthetically.
• Nonnatural amino acids can be incorporated into proteins chemically.
• Protein amino acid structure follows IUPAC-IUB conventions.

Protein Amino Acids and Peptide Bond

• Proteins are linear chains of L-amino acids connected by peptide bonds.
• L-amino acids have unique features contributing to protein structure and function.
• Many post-translational modifications of amino acids occur during synthesis and degradation.

Residue Structures

• Each residue is listed with three- and one-letter codes along with their respective structures.

Experimental Approaches to Protein Covalent Structure Determination

• Protein chemical methods are essential for confirming protein structure and post-translational modifications.
• Mass spectrometric methods are increasingly crucial.

Post-translational Modifications: Terminal Groups

• The initial step of protein biosynthesis in bacteria involves the formation of a peptide bond between N-formyl-L-methionyl-tRNA and the second aminoacyl tRNA.
• N-terminal methionyl residues are often removed rapidly, and their removal is influenced by the identity of the adjacent residues.
• Proteins are further modified by acetylation or alkylation of the amino-terminal residue.

Acetylation

• The N-acetyl group is a common constituent of proteins.
• N-acetylation is a cotranslational event (occurring when the nascent peptide chain is about 40 residues long).
• Some mature proteins are acetylated post-translationally.

Fatty Acylation

• Amino-terminal glycine residues on many proteins are often fatty acylated (most commonly myristoyl).
• This modification influences protein-membrane association and protein-protein interactions.
• Other variants of fatty acylation involving C14:1, C14:2, and C12:0 are also common.

Pyroglutamyl

• Pyroglutamyl is formed by cyclization of N-terminal glutamine residues, potentially with or without enzymatic catalysis.

Other Acyl Groups

• Other acyl modifications like N-formyl glycine are found, though less frequently, in proteins, primarily in prokaryotic systems and are frequently associated with specific metabolic enzymes.

Glycosylation

• Glycosylation, the addition of carbohydrate chains to proteins, is common in extracellular proteins, particularly membrane-bound and secreted proteins.
• It's a crucial post-translational modification, often involving a branching glycan moiety, involving multiple steps leading to complex modifications.

Methylation

• Methylation of amino acid residues, particularly arginine, histidine, and lysine, is a post-translational modification observed in diverse proteins. Methylation modification affects protein structure and function in important ways.

Other Amino Acid Modification

• Hydroxylation: A modification of specific amino acids like proline (in collagen) that affects protein structure and function, particularly in extracellular matrix proteins. Specific sequences and types of hydroxylation are also significant.
• Cross-linking of amino acid residues to form stable bonds affects protein stability, interactions, and overall structure, important in structural proteins.
• Oxidation: The formation of disulfide bonds affects protein structure by linking cysteine residues, crucial for the stability and function of proteins, especially extracellular ones.
• Hydrolysis and Isomerization: Proteins are subject to hydrolysis, affecting certain amino acid residues like asparagine by deamidation or isomerization.
• Oligoglutamylation: A modification of glutamic acid residues where multiples, often varying in length or structure, are present.