Serine Proteases Overview
21 Questions
0 Views

Choose a study mode

Play Quiz
Study Flashcards
Spaced Repetition
Chat to lesson

Podcast

Play an AI-generated podcast conversation about this lesson

Questions and Answers

What amino acid residues are primarily involved as nucleophiles in aspartic proteases?

  • Ser, Cys, and sometimes Thr (correct)
  • Ser, Cys, and Thr
  • Asp, Glu, and Met
  • Lys, Arg, and His
  • Which characteristic distinguishes aspartic proteases from serine proteases?

  • Active site containing two aspartate residues (correct)
  • Active at neutral pH
  • Covalent catalysis of peptide bonds
  • Presence of a tetrahedral intermediate
  • What is the significance of the pH-dependence in the mechanism of aspartic proteases?

  • The mechanism is not affected by pH
  • One Asp must be protonated while the other is deprotonated (correct)
  • Only the substrate influences the pH dependency
  • Both Asp residues remain protonated
  • What is the role of protease inhibitors in the treatment of HIV?

    <p>They selectively inhibit HIV-1 protease to prevent new virus formation</p> Signup and view all the answers

    In the context of HIV-1 protease, which structural feature contributes to its function?

    <p>The homodimeric nature allows for genetic economy in the virus</p> Signup and view all the answers

    What class of enzymes do trypsin, chymotrypsin, and elastase belong to?

    <p>Serine proteases</p> Signup and view all the answers

    Which amino acid side chains are preferentially cleaved by trypsin?

    <p>carbonyl side of Arg or Lys</p> Signup and view all the answers

    What does the substrate-binding pocket of elastase primarily accommodate?

    <p>Small, neutral residues</p> Signup and view all the answers

    Which enzyme is specifically mentioned as not being a protease but is mechanistically similar?

    <p>Acetylcholinesterase</p> Signup and view all the answers

    What structural feature is common to the serine proteases like trypsin, chymotrypsin, and elastase?

    <p>Catalytic triad involving Asp, His, and Ser</p> Signup and view all the answers

    What distinguishes the specificity of chymotrypsin from trypsin?

    <p>Chymotrypsin cleaves at the aromatic carbonyl side of Phe or Tyr</p> Signup and view all the answers

    Which protease participates in the blood clotting cascade?

    <p>Thrombin</p> Signup and view all the answers

    How does the catalytic site of serine proteases function in the context of substrate interaction?

    <p>It utilizes a peptide segment from the substrate for catalysis</p> Signup and view all the answers

    What is the primary function of Asp102 in the chymotrypsin mechanism?

    <p>To orient His57 and form a low-barrier hydrogen bond</p> Signup and view all the answers

    Which component stabilizes the tetrahedral oxyanion intermediate in chymotrypsin?

    <p>Backbone N-H groups of Gly193 and Ser195</p> Signup and view all the answers

    What type of catalysis is suggested by the presence of a covalent bond in the chymotrypsin mechanism?

    <p>A mixture of covalent and general acid-base catalysis</p> Signup and view all the answers

    Which step in the chymotrypsin mechanism is characterized as a 'burst kinetics' phenomenon?

    <p>The collapse of the tetrahedral intermediate</p> Signup and view all the answers

    What is indicated by the term 'oxyanion hole' in the chymotrypsin mechanism?

    <p>The stabilization of the tetrahedral intermediate</p> Signup and view all the answers

    Which residues are typically involved in the catalytic triad in hydrolases and transferases?

    <p>Asp, Glu, and His</p> Signup and view all the answers

    In chymotrypsin kinetics, what does the observation of burst kinetics suggest about the reaction steps?

    <p>The first step is fast, followed by a slow second step</p> Signup and view all the answers

    What does His57 primarily function as in the chymotrypsin mechanism?

    <p>A general acid and base</p> Signup and view all the answers

    Study Notes

    Serine Proteases

    • Trypsin, chymotrypsin, elastase, thrombin, subtilisin, plasmin, and tissue plasminogen activator are all serine proteases.
    • They are secreted as proenzymes or zymogens.
    • Serine proteases cleave polypeptide chains.
    • They have similar sequences, structures, and mechanisms.
    • Acetylcholinesterase also has a similar mechanism to serine proteases, but is not a protease.

    Trypsin, Chymotrypsin and Elastase

    • Trypsin cleaves after Arg or Lys (basic amino acids) except when either is followed by Pro.
    • Chymotrypsin cleaves after Phe or Tyr (aromatic amino acids).
    • Elastase cleaves after small, neutral amino acid residues.

    Structure

    • Chymotrypsin (and other serine proteases) contains a catalytic triad, which is composed of Asp, His, and Ser.

    Substrate Binding Pocket

    • The nature of the pocket determines the specificity of the enzyme.
    • Trypsin has a negatively charged substrate-binding pocket for basic residues.
    • Chymotrypsin has a hydrophobic pocket to bind aromatic residues.
    • Elastase has a bulky substrate-binding pocket with Thr and Val residues to accommodate small amino acids.

    Chymotrypsin Kinetics

    • Chymotrypsin kinetics exhibit burst kinetics- this suggests a fast initial step and a slow second step.
    • Burst kinetics are assayed using an artificial substrate that releases a product that absorbs at 400 nm.

    Serine Protease Mechanism

    • Serine proteases use a combination of covalent and general acid-base catalysis.
    • The catalytic triad works as follows:
      • Asp orients and stabilizes His.
      • His acts as a general acid and base.
      • Ser195 forms a covalent bond with the peptide to be cleaved, changing the trigonal carbon to tetrahedral.
      • The tetrahedral oxyanion intermediate is stabilized by Gly193 and Ser195.
      • The oxyanion hole is composed of two amide groups.

    Catalytic Triads

    • Found in several hydrolases and transferase enzymes.
    • Involve divergent and convergent evolution
      • Residues are far away in the primary structure.
    • Catalytic triads are composed of:
      • Acid that orients and stabilizes the base (Asp, Glu, His)
      • Base that polarizes the nucleophile (His, rarely Lys)
      • Nucleophile that attacks the substrate (Ser, Cys, sometimes Thr)

    Aspartic Proteases

    • Aspartic proteases have a different structure and mechanism than serine proteases.
    • They contain two Asp residues in the active site.
    • They cleave peptide bonds between two hydrophobic amino acids.
    • They do not involve covalent catalysis.

    pH Dependence of Aspartic Proteases

    • Aspartic proteases are active at acidic pH.
    • The mechanism requires that one Asp is protonated and the other is deprotonated when the substrate binds.
    • The LBHB allows 'hydrogen tunneling'.

    HIV-1 Protease

    • A novel aspartic protease, HIV-1 protease, cleaves polyprotein products of the HIV genome.
    • It is also a remarkably good imitation of mammalian aspartic proteases.
    • HIV-1 protease is a homodimer, which makes it more genetically economical for the virus.
    • It has a two-fold symmetric active site with different 'flaps'.

    Protease Inhibitors for AIDS Patients

    • Protease inhibitors are a common treatment for AIDS.
    • They block the active site of HIV-1 protease so new viral particles cannot be created.
    • Structure-based drug design has been used to create several inhibitors that work in a dish.

    Studying That Suits You

    Use AI to generate personalized quizzes and flashcards to suit your learning preferences.

    Quiz Team

    Related Documents

    Description

    Explore the fascinating world of serine proteases, including trypsin, chymotrypsin, and elastase. This quiz delves into their structures, mechanisms, and specificity in cleaving polypeptide chains. Test your knowledge on these essential enzymes and their catalytic functions.

    More Like This

    Use Quizgecko on...
    Browser
    Browser