Binary and ternary complexes involving small molecules and carbonyl reductase

CHED 780

Matthew T. Mayer, mattmayer@mail.boisestate.edu and Henry A. Charlier Jr., hcharlier@chem.boisestate.edu. Department of Chemistry and Biochemistry, Boise State University, 1910 University Drive, Boise, ID 83725-1520
Carbonyl reductase (CR) is an enzyme that catalyzes the NADPH-dependent reduction of various carbonyls. CR has been implicated in the cardiotoxicity often observed in cancer patients after treatment with anthracycline drugs. Given the role of CR in the cardiotoxicity, it is important to fully understand the enzyme's structure and function. The present study examines how CR binds small molecules, including known inhibitors of CR. Using fluorimetry, the binding of several enzyme-small molecule complexes were studied. NADPH and NADP+ were found to bind to the free enzyme with µM affinities. NADP+ and the fluorescent probe 8-anilino-1-naphthalenesulfonic acid (ANS) were found to bind CR simultaneously without competing. This information, coupled with the knowledge that ANS does not inhibit CR, suggests the presence of a ligand binding site other than the active site of the enzyme, which may have implications for CR inhibition. NIH/P20RR016454, NIH/R15CA102119-01
 

Undergraduate Research Poster Session: Biochemistry
2:00 PM-4:00 PM, Monday, April 7, 2008 Morial Convention Center -- Hall A, Poster

Division of Chemical Education

The 235th ACS National Meeting, New Orleans, LA, April 6-10, 2008