Bradley Kossmann

Georgia State University | GSU · Department of Chemistry

Tyrosyl-DNA phosphodiesterase 2 (TDP2) processes protein/DNA adducts resulting from abortive DNA topoisomerase II (Top2) activity. TDP2 inhibition could provide synergism with the Top2 poison class of chemotherapeutics. By virtual screening of the NCI diversity small molecule database, we identified selective TDP2 inhibitors and experimentally veri...

Replicative DNA polymerases (Pols) frequently possess two distinct DNA processing activities - DNA synthesis (polymerization) and proofreading (3'-5' exonuclease activity). The polymerase and exonuclease reactions are performed alternately and are spatially separated in different protein domains. Thus, the growing DNA primer terminus has to undergo...

PolB domains are colored as follows: N-terminal domain in light blue; exonuclease domain in green; palm domain in cyan; fingers domain in gold and thumb domain in red. PCNA and DNA are shown in grey and black.

PolB domains are colored as follows: N-terminal domain in light blue; exonuclease domain in green; palm domain in cyan; fingers domain in gold and thumb domain in red. PCNA and DNA are shown in grey and black. The hinge region is highlighted in yellow.

Contact residues are explicitly shown in ball and stick representation. Contact types are colored as follows: Salt-bridges in light blue and red; persistent hydrogen bonds (other than salt bridges) in cyan and dark blue; hydrophobic interaction in green and purple.

Contact residues are explicitly shown in ball and stick representation. Contact types are colored as follows: Salt-bridges in light blue and red; persistent hydrogen bonds (other than salt bridges) in cyan and dark blue; hydrophobic interaction in green and purple.

Only the palm and thumb domains of PolB are shown for clarity.

Many genomes contain families of paralogs—proteins with divergent function that evolved from a common ancestral gene after a duplication event. To understand how paralogous transcription factors evolve divergent DNA specificities, we examined how the glucocorticoid receptor and its paralogs evolved to bind activating response elements [(+)GREs] and...

Phospholipids (PLs) are unusual signaling hormones sensed by the nuclear receptor liver receptor homolog 1 (LRH 1), which has evolved a novel allosteric pathway to support appropriate interaction with coregulators depending on ligand status. LRH-1 plays an important role in controlling lipid and cholesterol homeostasis and is a potential target for...

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Author Summary DNA repair efficiency is critically dependent on the function of DNA glycosylases. These versatile enzymes perform a remarkably discriminating search for DNA lesions, followed by damage-specific base extrusion into to the enzyme's active site and removal of the damaged bases. Our work elucidates the mechanism of Bacillus cereus AlkD,...