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Surface Mutation Thr34His Facilitates Purification of Haemophilus influenza Carbonic Anhydrase via Metal Affinity Chromatography
Chemistry & Biochemistry Student Scholarship
  • Caroline Foley, Providence College
  • Dr. Kathleen Cornely, Providence College
Description

In order to pursue Haemophilus influenza carbonic anhydrase (HICA) as a potential drug target, easy and efficient purification methods must be developed. While immobilized metal affinity chromatography (IMAC) may be used, complications with polyhistidine tags is a concern. Inspired by the endogenous metal affinity of Escherichia coli β-carbonic anhydrase (ECCA), we suggest that the generation of histidine clusters on HICA’s surface will facilitate its purification by metal affinity chromatography without the potential interference of His-tags. Here we investigate the Thr34His mutation as a method to generate metal affinity in HICA. Since Thr34His is located only 5.3 Å away from His32, the two residues make a vicinal histidine pair that can interact with nickel resin. We report successful generation of Thr34His HICA mutant plasmid via site-directed mutagenesis. To obtain mutant protein for metal affinity chromatography, Thr34His HICA was overexpressed in E. coli cells and isolated as a cell lysate with a concentration of 20.2 ± 0.6 mg/mL. Metal affinity chromatography was performed on the sample, and the chromatography fractions were analyzed by SDS-PAGE in order to assess the metal affinity of the mutant. SDS-PAGE revealed that while Thr34His HICA eluted at low 10 mM and 25 mM concentrations of imidazole, 150 mM imidazole was required to fully elute the mutant. These results suggest that through the generation of surface histidine pairs, HICA can be engineered to have metal affinity and thus be easily purified via IMAC.

Publisher
Providence College
Date
5-13-2017
Type
Article
Format
Text
.pdf
Language
English
Citation Information
Caroline Foley and Dr. Kathleen Cornely. "Surface Mutation Thr34His Facilitates Purification of Haemophilus influenza Carbonic Anhydrase via Metal Affinity Chromatography" (2017)
Available at: http://works.bepress.com/kathleen-cornely/22/