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Loyola University Chicago

Chemistry: Faculty Publications and Other Works

Antibiotics

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Full-Text Articles in Physical Sciences and Mathematics

The Dimerization Domain In Dape Enzymes Is Required For Catalysis, Boguslaw Nocek, Anna Starus, Magdalena Makowska-Grzyska, Blanca Gutierrez, Stephen Sanchez, Robert Jedrzejczak, Jamey C. Mack, Kenneth W. Olsen, Andrzej Joachimiak, Richard C. Holz May 2014

The Dimerization Domain In Dape Enzymes Is Required For Catalysis, Boguslaw Nocek, Anna Starus, Magdalena Makowska-Grzyska, Blanca Gutierrez, Stephen Sanchez, Robert Jedrzejczak, Jamey C. Mack, Kenneth W. Olsen, Andrzej Joachimiak, Richard C. Holz

Chemistry: Faculty Publications and Other Works

The emergence of antibiotic-resistant bacterial strains underscores the importance of identifying new drug targets and developing new antimicrobial compounds. Lysine and meso-diaminopimelic acid are essential for protein production and bacterial peptidoglycan cell wall remodeling and are synthesized in bacteria by enzymes encoded within dap operon. Thereforedap enzymes may serve as excellent targets for developing a new class of antimicrobial agents. The dapE-encoded N-succinyl-L,L-diaminopimelic acid desuccinylase (DapE) convertsN-succinyl-L,L-diaminopimelic acid to L,L-diaminopimelic acid and succinate. The enzyme is composed of catalytic and dimerization domains, and belongs to the M20 peptidase family. To understand the specific role …


Lysine Biosynthesis In Bacteria: A Metallodesuccinylase As A Potential Antimicrobial Target, Danuta M. Gillner, Daniel P. Becker Ph.D., Richard C. Holz Feb 2013

Lysine Biosynthesis In Bacteria: A Metallodesuccinylase As A Potential Antimicrobial Target, Danuta M. Gillner, Daniel P. Becker Ph.D., Richard C. Holz

Chemistry: Faculty Publications and Other Works

In this review, we summarize the recent literature on dapE-encoded N-succinyl-l,l-diaminopimelic acid desuccinylase (DapE) enzymes, with an emphasis on structure–function studies that provide insight into the catalytic mechanism. Crystallographic data have also provided insight into residues that might be involved in substrate and hence inhibitor recognition and binding. These data have led to the design and synthesis of several new DapE inhibitors, which are described along with what is known about how inhibitors interact with the active site of DapE enzymes, including the efficacy of a moderately strong DapE inhibitor.