Engineering pH dependent binding interactions anti-caffeine VHH camelid antibodies with ionizable amino acid side chain substitutions

Session Number

Project ID: CHEM 04

Advisor(s)

Dr. James R. Horn; Northern Illinois University

Dr. Hyeyoung Eom; Northern Illinois University

Discipline

Chemistry

Start Date

22-4-2020 10:05 AM

End Date

22-4-2020 10:20 AM

Abstract

Protein engineering grows every day as more opportunities emerge to engineer proteins with specific functions. Engineering pH dependent proteins are of specific interest because they can then be used in various environments. With a goal of creating a reverse control switch for pH dependent proteins, a variety of mutations in anti-caffeine were created and studied, with particular interest in the mutant Y61D. Using isothermal titration calorimetry, the stoichometry, enthalpy, entropy, and binding constants were found in a variety of anti-caffeine VHH and caffeine interactions. A range of pHs from 4.0 to 7.4 were studied in appropriate buffers. By introducing aspartic and glutamic acid residues into the homodimer interface of the caffeine-anticaffeine, we were able to engineer pH-dependent proteins that bind well at low pHs.

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Apr 22nd, 10:05 AM Apr 22nd, 10:20 AM

Engineering pH dependent binding interactions anti-caffeine VHH camelid antibodies with ionizable amino acid side chain substitutions

Protein engineering grows every day as more opportunities emerge to engineer proteins with specific functions. Engineering pH dependent proteins are of specific interest because they can then be used in various environments. With a goal of creating a reverse control switch for pH dependent proteins, a variety of mutations in anti-caffeine were created and studied, with particular interest in the mutant Y61D. Using isothermal titration calorimetry, the stoichometry, enthalpy, entropy, and binding constants were found in a variety of anti-caffeine VHH and caffeine interactions. A range of pHs from 4.0 to 7.4 were studied in appropriate buffers. By introducing aspartic and glutamic acid residues into the homodimer interface of the caffeine-anticaffeine, we were able to engineer pH-dependent proteins that bind well at low pHs.