Substrates bind to an active site on the enzyme

This preview shows page 2 - 3 out of 3 pages.

Substrates bind to an active site on the enzyme. enzyme (E) + substrate (S) enzyme-substrate complex (ES) enzyme (E) + product (P) S P + + E ES E Enzyme Inhibition If an inhibitor is bound in the active site, then substrate can't bind. EI S E I +
Image of page 2

Subscribe to view the full document.

Many pharmaceutical drugs work by blocking the action of enzymes. Enzymes catalyze reactions by stabilizing the "transition state" of the reaction. Compounds that resemble the transition state should bind more tightly to the enzyme than reactants or products. These compounds can therefore serve as enzyme inhibitors (drugs). Example from page 7 of Lecture 35 notes: HIV Protease Inhibitors . Proteases inhibitors are used in treatment of HIV. Enzymes that cleave peptide bonds are called proteases. The overall mechanism of peptide bond cleavage - a type of displacement reaction- is shown below: O HO O - O C C C N OH + H 2 N N H H tetrahedral - OH intermediate Molecules with a stable tetrahedral atom at cleavage site will resemble the transition state and could bind more tightly to the enzyme than substrate does. Example of a molecule with a tetrahedral center: Approved drug for HIV, indinavir sulfate (The New England J. Med. 338, 1285 (1998)). Knowledge of reaction mechanism can lead to design of new therapeutic treatments. N N N O N Ph O H N OH HO H Ph = phenyl Interesting and important question - why doesn't this compound block all proteases? A second consideration is specificity. Tight binding is just one facet of drug design. Also must consider specificity and delivery.
Image of page 3
You've reached the end of this preview.

{[ snackBarMessage ]}

What students are saying

  • Left Quote Icon

    As a current student on this bumpy collegiate pathway, I stumbled upon Course Hero, where I can find study resources for nearly all my courses, get online help from tutors 24/7, and even share my old projects, papers, and lecture notes with other students.

    Student Picture

    Kiran Temple University Fox School of Business ‘17, Course Hero Intern

  • Left Quote Icon

    I cannot even describe how much Course Hero helped me this summer. It’s truly become something I can always rely on and help me. In the end, I was not only able to survive summer classes, but I was able to thrive thanks to Course Hero.

    Student Picture

    Dana University of Pennsylvania ‘17, Course Hero Intern

  • Left Quote Icon

    The ability to access any university’s resources through Course Hero proved invaluable in my case. I was behind on Tulane coursework and actually used UCLA’s materials to help me move forward and get everything together on time.

    Student Picture

    Jill Tulane University ‘16, Course Hero Intern