amino acids and proteins

• Amino Acids & Proteins

  
• SARS-CoV-2 spike monomer


  • FP, fusion peptide
  • HR1, heptad repeat 1
  • HR2, heptad repeat 2
  • IC, intracellular domain
  • NTD, N-terminal domain
  • SD1, subdomain 1
  • SD2, subdomain 2
  • TM, transmembrane region

  
• SARS-CoV-2 RBD


  • RBM sequence is shown in red
  • RBD core is shown in cyan
  • RBM in red
  • Disulfide bonds in the SARS-CoV-2 RBD are shown as sticks and indicated by arrows
  • N-terminal helix of ACE2 responsible for binding is labelled

  
• A new and highly pathogenic coronavirus (severe acute respiratory syndrome coronavirus-2, SARS-CoV-2) caused an outbreak in Wuhan city, Hubei province, China, starting from December 2019 that quickly spread nationwide and to other countries around the world
• The crystal structure of the receptor-binding domain (RBD) of the spike protein of SARS-CoV-2 bound to the cell receptor ACE2 was determined

  
• The overall ACE2-binding mode of the SARS-CoV-2 RBD is nearly identical to that of the SARS-CoV RBD, which also uses ACE2 as the cell receptor
• Structural analysis identified residues in the SARS-CoV-2 RBD that are essential for ACE2 binding, the majority of which either are highly conserved or share similar side chain properties with those in the SARS-CoV RBD

  
• Such similarity in structure and sequence strongly indicate convergent evolution between the SARS-CoV-2 and SARS-CoV RBDs for improved binding to ACE2, although SARS-CoV-2 does not cluster within SARS and SARS-related coronaviruses

  
• The epitopes of two SARS-CoV antibodies that target the RBD are also analysed for binding to the SARS-CoV-2 RBD, providing insights into the future identification of cross-reactive antibodies

  
• Glossary


  • Amide
  • Buffer
  • Cachexia
  • Conjugate
  • Homozygous
  • Kwashiorkor
  • Marasmus
  • Peptide bond
  • pH
  • Ampholyte

  
• General structure of α-Amino acids

  D & L isomerism of Amino acids

  
• The 20 commonly occurring amino acids can be grouped into 5 main classes based on properties of their R groups


  • Group #1: Non-polar, aliphatic amino acids are hydrophobic
  • Group #2: Tyr and Trp are much more polar than Phe
  • Group #3: Consider cysteine
  • Group #4: Consider histidine
  • Group #5: Consider serine, threonine and tyrosine

  
• • An important component of collagen
  • Found in myosin
  • Found in collagen
• Substituted amino acids


  Can you identify any reason why this substituted amino acid might be found in some proteins that bind Ca2+ (e.g. prothrombin)?

  
• Acid-Base Behaviour of Amino Acids

  • Amphoteric
  • Ampholyte - amphoteric electrolyte
  • pKa = negative log of the acid dissociation constant

  
• Buffer


  Buffers perform best when...
• Henderson-Hasselbalch Equation


  Consider an acid, HA
• Titration curve for Glycine

  1. Direction traveled in an electric field?

  2. Net charge at any given point?

  3. pI value?

  4. Where on the pH scale should the Zwitterion predominate?
• pI of an amino acid

  • The pI of an amino acid that contains only 2 dissociable groups is the mean of its two pKa values
  • For AAs that contain 3 dissociable groups, the pI lies between the pKa values on either side of the zwitterion
• Titration curve for Glutamic acid


  1. Identify the zwitterion

  2. Calculate the ratio of Form 3 to form 2 at pH 7.0

  3. Calculate the ratio of Form 3 to form 2 at pH 4.3

  
• Essential Amino Acids


  • Histidine
  • Isoleucine
  • Leucine
  • Lysine
  • Methionine
  • Phenylalanine
  • Threonine
  • Tryptophan
  • Valine

  
• Marasmus


  • Kwashiorkor
  • Cachexia
• Protein Diversity


  • Structural proteins
  • Antibodies
  • Catalysts
  • Motor proteins
  • Transport proteins
  • Receptor proteins
  • Signaling proteins
• Peptide Bonds


  • The linear sequence of AAs in a polypeptide (ppept) chain is called the primary structure
  • The linkage formed between AAs is a secondary amide bond called a peptide bond
  • Groups involved in peptide bonds carry no charges –and are NOT ionizable (do not contain labile hydrogens)
  • Buffering capacity of ppepts and proteins determined by...

  
• Types of proteins


  • Structural proteins
  • Antibodies
  • Catalysts
  • Motor proteins
  • Transport proteins
  • Receptor proteins
  • Signaling proteins
• Protein diversity
• The linear sequence of AAs in a polypeptide (ppept) chain is called the primary structure
• The linkage formed between AAs is a secondary amide bond called a peptide bond
• Groups involved in peptide bonds carry no charges and are NOT ionizable (do not contain labile hydrogens)
• Note that the residues are named with -yl endings
• Buffering capacity of ppepts and proteins determined by
• pH can affect the solubility of a protein
• pH can affect the shape of a protein
• pH can affect the activity of an enzyme
• Dipeptides, tripeptides, tetra, etc, oligopeptides, peptides, polypeptides and proteins

  Many peptides have biological functions e.g. the hormones insulin, vasopressin and oxytocin
• Changing one or even a few AAs may have no effect on the overall function of the protein
• Normal adult hemoglobin has 2 alpha chains and 2 beta chains
• A change at only a single AA residue (GluVal) in the β chain (146 AAs) is severe enough to cause a high death rate in the homozygous state
• Primary structure relates to both the AA sequence as well as the AA composition of a protein
• Alpha Helix


  • An α-helix may be right- or left-handed
  • Those found in proteins are almost always right-handed
  • Those found in nature typically have 3.5-3.7 residues per turn