College Seminar Series:  Dr. Shuaihua Gao

Please find the attached seminar flyer for Dr. Shuaihua Gao.

Identification, Structural Insights, and Protein Evolution of an Enantioselective Lactamase and Structural Dynamics of a TIM Barrel Protein Adenosine Deaminase

My talk includes two parts. Part one focuses on a newly discovered γ-lactamase. Abacavir, a carbocyclic 2′-deoxyguanosine nucleoside analogue, is an important chemotherapeutic agent in the cocktail therapy for HIV infection. One of the key steps in the biosynthesis of abacavir is the resolution of the bicyclic synthon (rac)-Vince-lactam (2-azabicyclo [2.2.1] hept-5-en-3-one), separating the enantiomers from the racemic entity. A type of hydrolase called γ-lactamase has demonstrated potential in developing a biocatalytic process to afford optically pure γ-lactam enantiomer. I have discovered a new type of γ-lactamases via high-throughput colorimetric screening to expand the diversity of γ-lactamases. I then investigated the hydrolytic mechanism and enantioselectivity origin via X-ray crystallography and molecular dynamics (MD) simulations. Finally, protein engineering was conducted to enhance the catalytic performances including enantioselectivity and thermostability. The long-term goal of this series of study is to provide a cost-effective approach to prepare optical isomer precursor for carbocyclic nucleosides type antiviral drugs.

Part two focuses on the spatial resolution structural dynamics for a TIM barrel protein adenosine deaminase (ADA) using temperature dependent hydrogen deuterium exchange coupled with mass spectrometry (TDHDX-MS). How enzymes are thermally activated is elusive. I believe that enzymes have evolved to embed structural dynamics (thermal activation networks) information within their structural scaffolds for efficient catalysis. To uncover regions of a protein for heat transfer, I have conducted a series of TD-HDX studies on a prototypic TIM barrel protein adenosine deaminase. TD-HDX is an emerging biophysical probe to interrogate protein dynamics for many biosystems. It produces temperature dependent and spatial resolution protein dynamics for individual peptides across the whole protein sequence. Mapping the dynamic perturbations on the protein structure upon mutation and ligand binding provides invaluable information on how fine-tuned dynamics across the protein structure of ADA govern the precise positioning of reactants in enzyme active site for efficient catalysis.

Wednesday, January 25th


2680 EHSEB

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Meeting ID: 984 6051 4814

Passcode: 690171


Emily Williams

Administrative Program Coordinator

Medicinal Chemistry | College of Pharmacy

The University of Utah

30 South 2000 East #306 | Salt Lake City, UT 84112


Published in All College of Pharmacy, Seminars