Chemistry Seminar - Studies of an Antibiotic Target
Structural and functional studies of the antibiotic target L,L-diaminopimelate aminotransferase from Verrucomicrobium spinosumDr. André HudsonProfessor and HeadThomas H. Gosnell School of Life Sciences, RITAbstract:Chlamydia trachomatis, the causative agent of the sexually transmitted infection chlamydia, uses the diaminopimelate aminotransferase pathway to synthesize the essential amino acid L-lysine. Essential enzyme in plants, we hypothesize that L,L-Diaminopimelate aminotransferase (DapL) is also essential in bacteria that employ this enzyme as the sole route to synthesize L-lysine via and is therefore an attractive enzymatic target for the development of narrow-spectrum antibiotics. The bacterium Verrucomicrobium spinosum is the closest free-living relative of bacteria from the genus Chlamydia, and utilizes the same pathway. Here we present the crystal structure of DapL from V. spinosum. The enzyme adopts a homodimeric structure, in line with previously reported type I aminotransferase enzymes, in addition to other diaminopimelate aminotransferases. Structural analyses of the enzyme facilitated by biophysical experiments, including analytical ultracentrifugation and small angle X-ray scattering, confirm that the oligomeric state is a dimer. However, the analyses also indicate the presence of a monomer-dimer equilibrium at lower enzyme concentrations, which has not been reported in other structurally characterized DapL orthologs.Speaker Bio:Dr. Hudson was born on the island of Jamaica and grew up in the town of Savanna-La-Mar in the parish of Westmoreland. He came to the United States at the age of 14 and completed High School at Salesian High in New Rochelle, NY. He received a B.S. in Biology from Virginia Union University (VUU) in 2000. He fell in love with science as an undergraduate student researcher in the laboratory of Dr. Anthony Madu at VUU where he performed research aimed at identifying pathogenic bacteria from fresh farm produce. He completed his PhD in the department of Plant Biology and Pathology in 2006 under the direction of Dr. Thomas Leustek at Rutgers University.Dr. Hudson joined the faculty in the Thomas H. Gosnell School of Life Sciences in the Fall of 2008 following a post-doctoral fellowship at Rutgers. He is a member of Alpha Phi Alpha Fraternity, Inc. (Gamma Chapter-VUU Spring 1998). He loves music (authentic reggae-Bob Marley, Peter Tosh, Burning Spear etc.), reading (autobiographies), chess and sports (football-Bills), (soccer-Brazil), (baseball-Yankees), (basketball-Knicks). He resides in Hilton New York with his wife Candice who is an English as a New Language (ENL) teacher at Northwood Elementary (Hilton, NY) and his son Michael (12).
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