Thomas Smith, PhD
Professor, Department of Biochemistry & Molecular Biology
Tel: (409) 772-6028
Campus Location: 5.104D Basic Science Bldg
Mail Route: 0645
Pubmed Publications | Lab Webpage
The Smith Lab is currently working on the structures (cryo-EM and crystallographic) of a number of viruses, ABC transporters, carbohydrate recognition complexes, enzymes, and are using biochemical methods to protect crops with antifungal proteins.
Glutamate Dehydrogenase and Insulin Disorders
Mammalian glutamate dehydrogenase (GDH) is a mitochondrial enzyme that catalyzes the reversible oxidative deamination of L-glutamate to 2-oxoglutarate
using NAD(P)+ as coenzyme. The enzyme is a homohexamer that is tightly regulated by a large number of positive and negative allosteric effectors as well as by cooperative interactions between subunits. While the enzyme is found in all organisms, this
regulation is only found in the animal form. In collaboration with Charles Stanley's laboratory, we found that elimination of an inhibitory (GTP binding) site causes hyperinsulinism/hyperammonemia (HHI). Most interestingly, we found that compounds
from green tea are effective in controlling HHI in transgenic mice expressing the defective human form of GDH.
Human rhinovirus is one of the major causes of the common cold. There are over 100 serotypes of this virus, making it unlikely that there will ever be a traditional vaccine for the common cold using conventional
vaccine methods. The Smith lab has examined the neutralization and dynamics of this virus to better understand how antibodies block infection and how to make more efficacious and novel vaccines.
We have determined the structures of antifungal proteins, KP4 and KP6, that are expressed by viruses that persistently infect Ustilago maydis. While KP4 acts by blocking voltage gated calcium channels in the target
fungi, the mode of action of KP6 is unclear other than it lyses the target cell. Since both KP4 and KP6 affect other Ustilago maydis, it may be possible to leaverage these proteins to treat human pathogens as well.
We have determined the structures of a number of ion binding domains from the ABC transporters of Synechocystis 6803. In our first study, determined the structure of the periplasmic domain of a zinc transporter,
ZnuA investigated structural aspects of the protein that may be involved in import regulation. Bioavailable iron is a limiting nutrient for primary production in large areas of the oceans. We determined the atomic structure of the ferric binding protein,
FutA, and examined the conformational changes in the protein as it binds metal. Cyanobacteria are the most abundant microorganisms in aquatic environments and play a key role in the global carbon cycle. To better understand how it concentrates CO2, we determined the atomic structure of the bicarbonate binding protein, CmpA. Having already determined the structure of a nitrate transporter, NrtA, we found clues to how these proteins are remarkably selective and how they may have 'cross talk' regulation.
Carbohydrate binding and processing proteins
Our gut microbiota recognize and process undigestible carbohydrates in the human gut. To better understand how they are able to process such a diverse collection of polysaccharides, we
determined the structures of a number of bacterial proteins that bind (SusD and Bt1043) and process (SusG) these carbohydrates.