Dave Leonard Lab: Publications and Presentations

Publications

Thomas M. HarperCynthia M. June, Magdalena A. Taracila, Robert A. Bonomo, Rachel A. Powers, David A. Leonard.   Multiple substitutions lead to increased loop flexibility and expanded specificity in Acinetobacter baumannii carbapenemase OXA-239. 2017 Biochemical Journal, in press.

Cynthia M. June, Taylor J. Muckenthaler, Emma C. Schroder, Zachary L. Klamer, Zdzislaw Wawrzak, Rachel A. Powers, Agnieszka Szarecka, David A. Leonard.  The structure of a doripenem-bound OXA-51 class D β-lactamase variant with enhanced carbapenemase activity.  2016 Protein Science, 25, 2152–2163.  [Pubmed]

Emma C. Schroder, Zachary L. Klamer, Aysegul Saral, Kyle A. Sugg, Cynthia M. June, Troy Wymore, Agnieszka Szarecka and David A. Leonard.  Clinical Variants of the Native Class D β-lactamase of Acinetobacter baumannii pose an emerging threat through increased hydrolytic activity against carbapenems.  2016  Antimicrobial Agents and Chemotherapy, 60, 6155-6164. [Pubmed]

Saral, A., Leonard, D. A., Duzgun, A. O., Cicek, A. C., June, C. M., and Sandalli, C. Kinetic characterization of GES-22 β-lactamase harboring the M169L clinical mutation, 2016 J Antibiot (Tokyo) 69, 858-862.  [Pubmed]

Joshua M. Mitchell, Jozlyn R. Clasman, Cynthia M. June, Kip-Chumba J. Kaitany, James R. LaFleur, Magdalena A. Taracila, Neil V. Klinger, Robert A. Bonomo, Troy Wymore, Agnieszka Szarecka, Rachel A. Powers and David A. Leonard.   The structural basis of activity against aztreonam and extended spectrum cephalosporins for two carbapenem-hydrolyzing class D β-lactamases from Acinetobacter baumannii.  2015 Biochemistry, 54:1976-1987.  [Pubmed].

Joshua M. Mitchell and David A. Leonard. Common clinical substitutions enhance the carbapenemase activity of OXA-51-like class D β-lactamases from Acinetobacter spp. 2014 Antimicrobial Agents and Chemotherapy, 58, 7015-7016. [Pubmed].

Cynthia M. June, Robert M. Vaughan, Lucas S. Ulberg, Robert A. Bonomo, Laurie A. Witucki and David A. Leonard. A fluorescent carbapenem for structure function studies of penicillin-binding proteins, β-lactamases and β-lactam sensors, 2014 Analytical Biochemistry, 463, 70-74. [ Pubmed].

Kip-Chumba Kaitany, Neil V. Klinger, Cynthia M. June, Maddison E. Ramey, Robert A. Bonomo, Rachel A. Powers and David A. Leonard. Structures of the Class D Carbapenemases OXA-23 and OXA-146: Mechanistic Basis of Activity Against Carbapenems, Extended-Spectrum Cephalosporins and Aztreonam, 2013 Antimicrobial Agents and Chemotherapy, 57(10), pp 4848-4855. [Pubmed]

David A. Leonard , Robert A. Bonomo, Rachel A. Powers . Class D β-lactamases: A Re-appraisal After Five Decades. 2013 Accounts in Chemical Research, 46 (11), 2407-2415 [Pubmed].

Jennifer S. Buchman, Kyle D. Schneider, Aaron R. Lloyd, Stephanie L. Pavlish and David A. Leonard. Site-saturation mutagenesis of position V117 in OXA-1 β-lactamase: the effect of side-chain polarity on enzyme carboxylation and substrate turnover . 2012 Biochemistry, 51 (14), pp 3143-3150. [Pubmed]

Kyle D. Schneider, Caleb J. Ortega, Nicholas A. Renck, Robert A. Bonomo, Rachel A. Powers and David A. Leonard. Structures of the class D carbapenemase OXA-24 from Acinetobacter baumannii in complex with doripenem. 2011 Journal of Molecular Biology, 406, 583-594. [Pubmed]

Kyle D. Schneider, Mary E. Karpen, Robert A. Bonomo, David A. Leonard, and Rachel A. Powers. The 1.4 Å crystal structure of the class D β-lactamase OXA-1 complexed with doripenem. 2009 Biochemistry, 48, 11840-11847. [Pubmed].

Kyle D. Schneider, Christopher R. Bethel, Anne M. Distler, Andrea M. Hujer, Robert A. Bonomo and David A. Leonard. Mutation of the active site carboxy-lysine (K70) of OXA-1 β-lactamase results in a deacylation-deficient enzyme. 2009 Biochemistry 48, 6136-6145. [Pubmed]

David A. Leonard, Andrea M. Hujer, Brian Smith, Kyle Schneider, Christopher R. Bethel, Kristine M. Hujer, Robert A. Bonomo The role of OXA-1 β-lactamase aspartate 66 in stabilization of the active site carbamate and substrate turnover. 2008 Biochem. J. 410, 455-462. [Pubmed]

Cover

Kyle Schneider's structure of OXA-1 with doripenem bound was featured on the cover of Biochemistry from January-March 2010.

Presentations

Kevin C. Chui, Cynthia M. June, Bradley J. Wallar, David A. Leonard.  Mutations at Arginine-148 in the ADC-7 Cephalosporinase Confer the Ability to Hydrolyze Cefepime.  38th Midwest Enzyme Chemistry Conference, Northwestern University, October 20, 2018.

Jonika Forbes-Benjamin, Cynthia M. June, Joshua M. Mitchell, Rachel A. Powers and David A. Leonard.  OXA-139:  A class D β-lactamase clinical variant from Acinetobacter baumannii that possesses an unusually high turnover rate for cephalosporins.   31st Annual Symposium of the Protein Society, Montreal QC, July, 26 2017.

Cynthia M. June, Christopher P. Russell, Emma C. Schroder, Rachel A. Powers, Agnieszka Szarecka and David A. Leonard.  X-ray crystallography reveals mechanism for two gain-of-function clinical variant carbapenemases from Acinetobacter baumannii.  31st Annual Symposium of the Protein Society, Montreal QC, July, 24 2017.

Emma C. Schroder, Zachary Klamer, Aysegul Saral, Kyle A. Sugg, Cindy M. June, Agnieszka Szarecka and David A. Leonard.  Multiple Active Site Substitutions in the Native Class D β-lactamase of Acinetobacter baumannii, OXA-51/66, Result in Increased Hydrolytic Activity Toward Carbapenems.  ASM Microbe 2016, Boston, MA, June 18, 2016.

Thomas M. Harper, Cynthia M. June, Rachel A. Powers and David A. Leonard. A triple-substitution clinical variant of OXA-23 carbapenemase from Acinetobacter baumannii shows increased activity toward cephalosporins and aztreonam.  250th National Meeting of the American Chemical Society, Boston, MA, August 19, 2015.

Cynthia M. June, Kyle A. Sugg, Emma C. Schroder, Rachel A. Powers and David A. Leonard. The Structure of OXA-51, the native carbapenemase of Acinetobacter baumannii, reveals insights into gain-of-function clinical variants. 250th National Meeting of the American Chemical Society, Boston, MA, August 19, 2015.

Thomas M. Harper, Jozlyn R. Clasman, Cynthia M. June, Rachel A. Powers, and David A. Leonard. Characterization of the Carbapenemase OXA-239. 34th Midwest Enzyme Chemistry Conference, Chicago Illinois, September 27, 2014.

Joshua M. Mitchell and David A. Leonard. Common clinical substitutions enhance the carbapenemase activity of OXA-51-like class D β-lactamases from Acinetobacter spp. 28th Annual Symposium of the Protein Society, San Diego, CA, July 27, 2014.

Jozlyn R. Clasman, Cynthia M. June, Brianna J. Jackman, Rachel A. Powers, and David A. Leonard. Biochemical basis for the extended spectrum cephalosporinase activity of a clinical AmpC β-lactamase variant. 28th Annual Symposium of the Protein Society, San Diego, CA, July, 27 2014.

Jozlyn R. Clasman, Joshua M. Mitchell, Kip-Chumba J. Kaitany, Neil V. Klinger, Vincent L. Baggett, Rachel A. Powers, and David A. Leonard. Crystal Structures of a Clinically-Derived Class D β-lactamase Variant with Cefotaxime, Ceftazidime, and Aztreonam Bound. 33rd Midwest Enzyme Chemistry Conference, Chicago Illinois, October 12, 2013.

Jozlyn R. Clasman, Joshua M. Mitchell, Kipchumba J. Kaitany, Neil V. Klinger, Cynthia M. June, Robert A. Bonomo, Rachel A. Powers, David. A. Leonard. Understanding the Structural Basis of Activity Against Aztreonam and Expanded-Spectrum Cephalosporins for Two Clinically-Derived Carbapenem-Hydrolyzing Class D β-Lactamases in Acinetobacter spp. International Conference on Antibiotic Agents and Chemotherapy, Denver, September 2013.

Joshua M. Mitchell, Neil V. Klinger, Kip-Chumba Kaitany, Robert A. Bonomo, Rachel A. Powers and David A. Leonard. A Pro Ser mutation augments advanced generation cephaloporinase activity in both the OXA-23 and OXA-24 subfamilies. 23rd Enzyme Mechanism Conference, San Diego, CA, January 5, 2013.

Kip-Chumba Kaitany, Neil V. Klinger, Cynthia M. June, Maddison E. Ramey, Robert A. Bonomo, Rachel A. Powers and David A. Leonard. A Class D β-lactamase Clinical Variant with Activity Against Carbapenems, Ceftazidime and Aztreonam. 23rd Enzyme Mechanism Conference, San Diego, CA, January 5, 2013.

Neil V. Klinger, Vincent L. Baggett, Cynthia M. June, Maddison E. Ramey, Rachel A. Powers and David A. Leonard. Crystal Structure and Kinetic Characterization of the Class D Carbapenemase OXA-23. 23rd Enzyme Mechanism Conference, San Diego, CA, January 5, 2013.

Zachary T. Hundley, Neil V. Klinger, Rachel A. Powers and David A. Leonard. Two mutations are necessary to convert class D β-lactamase function to -lactam sensor function. 23rd Enzyme Mechanism Conference, San Diego, CA, January 5, 2013.

Joshua M. Mitchell, Neil V. Klinger, Kip-Chumba Kaitany, Robert A. Bonomo, Rachel A. Powers and David A. Leonard. A Pro>Ser mutation augments advanced generation cephaloporinase activity in both the OXA-23 and OXA-24 subfamilies. 32nd Midwest Enzyme Chemistry Conference, Chicago Illinois, October 13, 2012.

Neil V. Klinger, Jacob Z. Scheid, Rachel A. Powers and David A. Leonard. Four hydrophobic residues control substrate selectivity in the OXA-24 carbapenemase. 32nd Midwest Enzyme Chemistry Conference, Chicago Illinois, October 13, 2012.

Kip-Chumba Kaitany, Neil V. Klinger, Maddison Ramey, Robert A. Bonomo, Rachel A. Powers and David A. Leonard. A Class D β-lactamase clinical variant with activity against carbapenems, ceftazidime and aztreonam. 32nd Midwest Enzyme Chemistry Conference, Chicago Illinois, October 13, 2012.

Zachary T. Hundley, Neil V. Klinger, Rachel A. Powers and David A. Leonard. Two mutations are necessary to convert class D β-lactamase function to β-lactam sensor function. 32nd Midwest Enzyme Chemistry Conference, Chicago Illinois, October 13, 2012.

Robert M. Vaughan, Neil V. Klinger, Luke S. Ulberg, Rachel A. Powers and David A. Leonard A valine/leucine hydrophobic clamp controls the carbapenemase activity of OXA-24. 32nd Midwest Enzyme Chemistry Conference, Chicago Illinois, October 13, 2012.

Stephanie L. Pavlish, Aaron R. Lloyd, Caleb J. Ortega and David A. Leonard. Mutagenesis of Two Active Site Residues of the Class D β-lactamase OXA-24/40. 30th Midwest Enzyme Chemistry Conference, Chicago Illinois, October 16, 2010.

Kyle D. Schneider, Nicholas A. Renck, Federica Morandi, Fabio Prati, Robert A. Bonomo, Rachel A. Powers and David A. Leonard. The structure of the class D beta-lactamase OXA-40 with oxacillin and a transition state analog bound. International Conference on Antibiotic Agents and Chemotherapy, Boston, September 2010.

Nicholas J. Hefferan, Caleb J. Ortega and David A. Leonard. Synthesis and Characterization of the fluorescent β-lactams mant-ampicillin and mant-meropenem. 239th American Chemical Society National Meeting, San Francisco, March 22, 2010.

Kyle D. Schneider, Nicholas A. Renck, Robert A. Bonomo, David A. Leonard, and Rachel A. Powers. Comparison of the Crystal Structures of OXA-40 and OXA-1 in Complex with Doripenem. International Conference on Antibiotic Agents and Chemotherapy, San Francisco, September 2009

Kyle D. Schneider, Robert A. Bonomo, David A. Leonard, and Rachel A. Powers. Acyl-enzyme complex of the class D β-lactamase OXA-1 and doripenem. American Society of Biochemistry and Molecular Biology; New Orleans, LA; April, 2009.

Kyle D. Schneider, Chris J. Davis, Angela Bopra, Robert P. Smart and David A. Leonard. Synthesis and characterization of a Deacylation-Defective Mutant of the Class D β-Lactamase OXA-1, American Society of Biochemistry and Molecular Biology; San Diego, CA; April 5, 2008.

Jennifer S. Buchman, Lea Barthel and David A. Leonard. Exploring β-lactamase mechanisms through site saturation mutagenesis of OXA-1 at the valine 117 position, American Society of Biochemistry and Molecular Biology; San Diego, CA; April 5, 2008.

Angela M. Bopra and David A. Leonard. Defining the role of a unique omega-loop insertion in the class D β-lactamase OXA-1, American Society for Biochemistry and Molecular Biology National Meeting, Washington, DC, April 28-May 2, 2007.

Brian A. Smith and David A. Leonard. Kinetic analysis of a catalytically-compromised mutant of the class D β-lactamase OXA-1, American Society for Biochemistry and Molecular Biology National Meeting, Washington, DC, April 28-May 2, 2007.

Sarah Toman and David Leonard, Determining the affinity of Cibacron Blue 3 GA and 3-aminophenylboronic acid for the two lactamases OXA-1and TEM-1, American Chemical Society National Meeting, Chicago, Illinois, March 25-29, 2007.

Andrea M. Hujer, David A. Leonard, Chris R. Bethel and Robert A. Bonomo. An antibody capable of detecting and inhibiting OXA-1 β-lactamase. International Conference on Antibiotic Agents and Chemotherapy, San Francisco, September 2006.

David A. Leonard, Christopher R. Bethel, Andrea M. Hujer, Kristine M. Hujer, Robert A. Bonomo Defining the role of Asp66 in the Class D β-lactamase OXA-1, ASBMB National Meeting, San Francisco, April 2006