PROTEINS

• What intermediate is formed in the serine protease reaction mechanism?

  Acyl enzyme intermediate
• What happens to the acyl group in the serine protease reaction?

  It is hydrolyzed off the serine
• What types of catalysis occur during the serine protease reaction?

  Acid-base catalysis and transition state stabilization
• At what pH is the serine protease reaction inhibited?

  Low pH
• What is the pH optimum for serine protease reactions?

  At or slightly above neutrality
• How do metabolic pathways typically operate?

  • Via multiple enzyme-catalyzed steps
  • Substrates and products are channeled to next enzyme
  • Enhanced by multisubunit enzyme complexes
  • Can involve attachment to scaffolds or fusion into one polypeptide
• What is the role of lysosomes in protein degradation?

  They degrade endocytosed proteins and organelles
• What is the primary function of the proteasome?

  Degrade ubiquitinated proteins
• What is ubiquitin and its role in protein degradation?

  It targets proteins to the proteasome
• How is ubiquitin attached to a protein?

  Covalently to a lysine residue
• What happens during polyubiquitination?

  Multiple ubiquitin molecules attach to a protein
• What is the effect of ligand binding on protein activity?

  It triggers allosteric conformational changes
• What is the shape of the O2 binding curve for hemoglobin?

  Sigmoidal
• What does positive cooperativity in hemoglobin indicate?

  Affinity for O2 increases after initial binding
• What is the role of calcium ions in cell signaling?

  They act as important messengers
• What protein binds calcium ions to trigger activation?

  Calmodulin
• What conformational change occurs in calmodulin upon calcium binding?

  It undergoes a major allosteric transition
• What is the function of GTPase proteins like Ras?

  They regulate target protein activity
• What happens to GTPase proteins when they bind GTP?

  They adopt an active conformation
• What is the role of kinases in protein regulation?

  They carry out phosphorylation
• What is the effect of phosphorylation on protein activity?

  It can turn proteins on or off
• What occurs in the active site of an enzyme?

  • Substrate is transformed into product
  • Contains a catalytic site for reaction
  • Has a binding pocket for substrate specificity
• What is the kinetic equation for enzyme-catalyzed reactions?

  E + S ⇔ ES → E + P
• What is Vmax in enzyme kinetics?

  Maximal rate at high substrate concentrations
• What does the Michaelis-Menten equation describe?

  Relationship between substrate concentration and reaction rate
• What does a lower KM value indicate?

  Higher affinity of enzyme for substrate
• What is the significance of cellular metabolite concentrations near KM?

  Allows cells to respond to substrate concentration changes
• What do proteases do?

  Cleavage of peptide bonds in proteins
• What is the catalytic triad in serine proteases?

  Serine, aspartate, and histidine residues
• How do digestive proteases select cleavage sites?

  Based on features of their binding pockets
• What are the characteristics of neurodegenerative diseases related to protein misfolding?

  • Accumulation of insoluble misfolded proteins
  • Formation of pathological lesions (plaques)
  • Examples: Alzheimer's and mad cow disease
• What is the role of ligands in protein interactions?

  They bind to proteins and modify activity
• What is the significance of complementarity in ligand binding?

  Higher complementarity increases specificity and affinity
• What are complementarity-determining regions (CDRs) in antibodies?

  Regions that make specific contacts with antigens
• What are the key features of enzyme-catalyzed reactions?

  • Highly specific
  • Rate enhancements of 10^6 to 10^12
  • Not consumed in reactions
  • Do not change ∆G0' or Keq
• How do enzymes achieve rate enhancement?

  By stabilizing the transition state structure
• What is the primary structure of globin proteins?

  Mostly α helical secondary structure
• What does the similarity in globin structures indicate?

  Functional redundancy among amino acids
• What is the significance of the native conformation of a protein?

  It is the most stable structure
• What can cause protein denaturation?

  Heating or treatment with organic solvents