Cells exist in a state of continuous metabolic flux. The Krebs cycle, a central metabolic hub in the cell, is responsible for supplying precursors for the synthesis of amino acids, nucleotides, and compounds required for energy transfer. During periods of increased metabolic flux, metabolites in the Krebs cycle become depleted and must be replenished. Pyruvate carboxylase (PC), a multifunctional enzyme, replenishes the Krebs cycle by catalyzing the conversion of pyruvate to oxaloacetate, a Krebs cycle intermediate. The Shorewood SMART Team (Students Modeling A Research Topic) created a model of PC using 3D printing technology. PC contains four distinct domains: biotin carboxylase (BC), central allosteric, carboxyltransferase (CT), and biotin carboxyl carrier protein (BCCP). The overall reaction is initiated by BCCP‐biotin carboxylation in the BC domain. BCCP‐carboxybiotin physically translocates to the CT domain to transfer its carboxyl group to pyruvate. The active site of the CT domain undergoes a reconfiguration upon pyruvate binding to accommodate the docking of BCCP‐carboxybiotin for pyruvate carboxylation. With the rise in antibiotic resistance, understanding how PC functions may provide a target in developing new antibiotics, whereby the new drug would eliminate critical metabolic activity, thus killing the bacteria. Supported by a grant from the NIH‐CTSA UL1RR031973.

Cadmium (Cd2+) is a toxic metal found in the environment, a product of industrial pollution, and can enter the body through inhalation. Chronic exposure to Cd2+ causes kidney failure characterized by Fanconi‐like Syndrome, in which an array of sodium‐dependent nutrient transport is inhibited. Cd2+ causes a concentration‐dependent reduction in sodium‐glucose co‐transport that is correlated to the sodium‐glucose transporter (SGLT1) gene expression in kidney proximal tubule epithelial cells. SGLT1 is regulated by the zinc finger transcription factor, Sp1. In the presence of Cd2+, the zinc ion is displaced by a Cd2+ ion, resulting in the loss of transcriptional regulation of SGLT1. The structure of human SGLT1 is not known; as such the Shorewood SMART Team (Students Modeling A Research Topic) modeled a bacterial homolog of SGLT1 using 3D printing technology. The SGLT1 protein transmembrane helices (TM2E, TM3, TM7E, TM8, and TM11) and amino acids on these helices vital for Na+ dependent glucose co‐transport are conserved. SGLT1 undergoes a conformational change enabling Na+ dependent glucose transport across the apical membrane of proximal tubule of kidney. In order to understand the glucose transport in the face of Cd2+ and to understand the underlying molecular mechanism responsible for SGLT1 glucose transport, it is essential to know the protein structure of SGLT1. Supported by a grant from NIH‐SEPA and NIH‐CTSA