A Distal Disulfide Bridge in OXA-1 β-Lactamase Stabilizes the Catalytic Center and Alters the Dynamics of the Specificity Determining Ω Loop

Simakov, Nikolay; Leonard, David A.; Smith, Jeremy C.; Wymore, Troy; Szarecka, Agnieszka

doi:10.1021/acs.jpcb.6b07884

Title: A Distal Disulfide Bridge in OXA-1 β-Lactamase Stabilizes the Catalytic Center and Alters the Dynamics of the Specificity Determining Ω Loop

Journal Article · Mon Sep 26 00:00:00 EDT 2016 · Journal of Physical Chemistry. B, Condensed Matter, Materials, Surfaces, Interfaces and Biophysical Chemistry

DOI:https://doi.org/10.1021/acs.jpcb.6b07884· OSTI ID:1394366

Simakov, Nikolay ^[1]; Leonard, David A. ^[2]; Smith, Jeremy C. ^[3]; Wymore, Troy ^[4]; Szarecka, Agnieszka ^[2]

Carnegie Mellon Univ., Pittsburgh, PA (United States); Univ. at Buffalo, NY (United States)
Grand Valley State Univ., Allendale, MI (United States)
Oak Ridge National Lab. (ORNL), Oak Ridge, TN (United States)
Oak Ridge National Lab. (ORNL), Oak Ridge, TN (United States); Univ. of Michigan, Ann Arbor, MI (United States)

Widespread antibiotic resistance, particularly when mediated by broad-spectrum β-lactamases, has major implications for public health. Substitutions in the active site often allow broad-spectrum enzymes to accommodate diverse types of β-lactams. Substitutions observed outside the active site are thought to compensate for the loss of thermal stability. The OXA-1 clade of class D β-lactamases contains a pair of conserved cysteines located outside the active site that forms a disulfide bond in the periplasm. Here, the effect of the distal disulfide bond on the structure and dynamics of OXA-1 was investigated via 4 μs molecular dynamics simulations. The results reveal that the disulfide promotes the preorganized orientation of the catalytic residues and affects the conformation of the functionally important Ω loop. Furthermore, principal component analysis reveals differences in the global dynamics between the oxidized and reduced forms, especially in the motions involving the Ω loop. A dynamical network analysis indicates that, in the oxidized form, in addition to its role in ligand binding, the KTG family motif is a central hub of the global dynamics. As activity of OXA-1 has been measured only in the reduced form, we suggest that accurate assessment of its functional profile would require oxidative conditions mimicking periplasm.

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Research Organization:: Oak Ridge National Lab. (ORNL), Oak Ridge, TN (United States)

Sponsoring Organization:: USDOE; National Inst. of Health (NIH) (United States)

Grant/Contract Number:: AC05-00OR22725; P41GM103712-01

OSTI ID:: 1394366

Alternate ID(s):: OSTI ID: 1424461

Journal Information:: Journal of Physical Chemistry. B, Condensed Matter, Materials, Surfaces, Interfaces and Biophysical Chemistry, Vol. 121, Issue 15; ISSN 1520-6106

Publisher:: American Chemical SocietyCopyright Statement

Country of Publication:: United States

Language:: English

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Cited by: 5 works

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References (72)

The β-lactamase threat in Enterobacteriaceae, Pseudomonas and Acinetobacter Livermore, David M.; Woodford, Neil Trends in Microbiology, Vol. 14, Issue 9 https://doi.org/10.1016/j.tim.2006.07.008	journal	September 2006
Recommendations for the Management of Beta-Lactam Intolerance Macy, Eric; Ngor, Eunis Clinical Reviews in Allergy & Immunology, Vol. 47, Issue 1 https://doi.org/10.1007/s12016-013-8369-8	journal	April 2013
Molecular mechanisms of antibiotic resistance Blair, Jessica M. A.; Webber, Mark A.; Baylay, Alison J. Nature Reviews Microbiology, Vol. 13, Issue 1 https://doi.org/10.1038/nrmicro3380	journal	December 2014
Bacterial Resistance to β-Lactam Antibiotics: Compelling Opportunism, Compelling Opportunity ^† Fisher, Jed F.; Meroueh, Samy O.; Mobashery, Shahriar Chemical Reviews, Vol. 105, Issue 2 https://doi.org/10.1021/cr030102i	journal	February 2005
Three Decades of -Lactamase Inhibitors Drawz, S. M.; Bonomo, R. A. Clinical Microbiology Reviews, Vol. 23, Issue 1 https://doi.org/10.1128/CMR.00037-09	journal	January 2010
Updated Functional Classification of -Lactamases Bush, K.; Jacoby, G. A. Antimicrobial Agents and Chemotherapy, Vol. 54, Issue 3 https://doi.org/10.1128/AAC.01009-09	journal	December 2009
Class D β-Lactamases: A Reappraisal after Five Decades Leonard, David A.; Bonomo, Robert A.; Powers, Rachel A. Accounts of Chemical Research, Vol. 46, Issue 11 https://doi.org/10.1021/ar300327a	journal	July 2013
Diversity, Epidemiology, and Genetics of Class D -Lactamases Poirel, L.; Naas, T.; Nordmann, P. Antimicrobial Agents and Chemotherapy, Vol. 54, Issue 1 https://doi.org/10.1128/AAC.01512-08	journal	August 2009
b-Lactamase inhibitors Page, Malcolm G. P. Drug Resistance Updates, Vol. 3, Issue 2 https://doi.org/10.1054/drup.2000.0137	journal	April 2000
Comparative activities of clavulanic acid, sulbactam, and tazobactam against clinically important beta-lactamases Payne, D. J.; Cramp, R.; Winstanley, D. J. Antimicrobial Agents and Chemotherapy, Vol. 38, Issue 4 https://doi.org/10.1128/AAC.38.4.767	journal	April 1994
OXA -Lactamases Evans, B. A.; Amyes, S. G. B. Clinical Microbiology Reviews, Vol. 27, Issue 2 https://doi.org/10.1128/CMR.00117-13	journal	April 2014
Extended-Spectrum -Lactamases in the 21st Century: Characterization, Epidemiology, and Detection of This Important Resistance Threat Bradford, P. A. Clinical Microbiology Reviews, Vol. 14, Issue 4 https://doi.org/10.1128/CMR.14.4.933-951.2001	journal	October 2001
Carbapenemases: a problem in waiting? Livermore, David M.; Woodford, Neil Current Opinion in Microbiology, Vol. 3, Issue 5 https://doi.org/10.1016/S1369-5274(00)00128-4	journal	October 2000
Emerging carbapenemases: a global perspective Walsh, Timothy R. International Journal of Antimicrobial Agents, Vol. 36 https://doi.org/10.1016/S0924-8579(10)70004-2	journal	November 2010
OXA-163, an OXA-48-Related Class D β-Lactamase with Extended Activity Toward Expanded-Spectrum Cephalosporins Poirel, Laurent; Castanheira, Mariana; Carrër, Amélie Antimicrobial Agents and Chemotherapy, Vol. 55, Issue 6 https://doi.org/10.1128/AAC.00022-11	journal	March 2011
Structural Basis of Activity against Aztreonam and Extended Spectrum Cephalosporins for Two Carbapenem-Hydrolyzing Class D β-Lactamases from Acinetobacter baumannii Mitchell, Joshua M.; Clasman, Jozlyn R.; June, Cynthia M. Biochemistry, Vol. 54, Issue 10 https://doi.org/10.1021/bi501547k	journal	March 2015
Sequence-function-stability relationships in proteins from datasets of functionally annotated variants: The case of TEM β-lactamases Abriata, Luciano A.; M. Salverda, Merijn L.; Tomatis, Pablo E. FEBS Letters, Vol. 586, Issue 19 https://doi.org/10.1016/j.febslet.2012.07.010	journal	July 2012
Structural insights into the loss of penicillinase and the gain of ceftazidimase activities by OXA-145 β-lactamase in Pseudomonas aeruginosa Meziane-Cherif, D.; Bonnet, R.; Haouz, A. Journal of Antimicrobial Chemotherapy, Vol. 71, Issue 2 https://doi.org/10.1093/jac/dkv375	journal	November 2015
Protein stability promotes evolvability Bloom, J. D.; Labthavikul, S. T.; Otey, C. R. Proceedings of the National Academy of Sciences, Vol. 103, Issue 15, p. 5869-5874 https://doi.org/10.1073/pnas.0510098103	journal	March 2006
Evolution of an Antibiotic Resistance Enzyme Constrained by Stability and Activity Trade-offs Wang, Xiaojun; Minasov, George; Shoichet, Brian K. Journal of Molecular Biology, Vol. 320, Issue 1 https://doi.org/10.1016/S0022-2836(02)00400-X	journal	June 2002
Structural Bases of Stability–function Tradeoffs in Enzymes Beadle, Beth M.; Shoichet, Brian K. Journal of Molecular Biology, Vol. 321, Issue 2 https://doi.org/10.1016/S0022-2836(02)00599-5	journal	August 2002
A natural polymorphism in -lactamase is a global suppressor Huang, W.; Palzkill, T. Proceedings of the National Academy of Sciences, Vol. 94, Issue 16 https://doi.org/10.1073/pnas.94.16.8801	journal	August 1997
Genetic and Structural Characterization of an L201P Global Suppressor Substitution in TEM-1 β-Lactamase Marciano, David C.; Pennington, Jeanine M.; Wang, Xiaohu Journal of Molecular Biology, Vol. 384, Issue 1 https://doi.org/10.1016/j.jmb.2008.09.009	journal	December 2008
A secondary drug resistance mutation of TEM-1 -lactamase that suppresses misfolding and aggregation Sideraki, V.; Huang, W.; Palzkill, T. Proceedings of the National Academy of Sciences, Vol. 98, Issue 1 https://doi.org/10.1073/pnas.98.1.283	journal	January 2001
How Protein Stability and New Functions Trade Off Tokuriki, Nobuhiko; Stricher, Francois; Serrano, Luis PLoS Computational Biology, Vol. 4, Issue 2 https://doi.org/10.1371/journal.pcbi.1000002	journal	February 2008
Negative Epistasis and Evolvability in TEM-1 β-Lactamase—The Thin Line between an Enzyme's Conformational Freedom and Disorder Dellus-Gur, Eynat; Elias, Mikael; Caselli, Emilia Journal of Molecular Biology, Vol. 427, Issue 14 https://doi.org/10.1016/j.jmb.2015.05.011	journal	July 2015
Protein Quality Control in the Bacterial Periplasm Merdanovic, Melisa; Clausen, Tim; Kaiser, Markus Annual Review of Microbiology, Vol. 65, Issue 1 https://doi.org/10.1146/annurev-micro-090110-102925	journal	October 2011
Disulfide bond formation in prokaryotes: History, diversity and design Hatahet, Feras; Boyd, Dana; Beckwith, Jon Biochimica et Biophysica Acta (BBA) - Proteins and Proteomics, Vol. 1844, Issue 8 https://doi.org/10.1016/j.bbapap.2014.02.014	journal	August 2014
Disulfide Bond Formation and Cysteine Exclusion in Gram-positive Bacteria Daniels, Robert; Mellroth, Peter; Bernsel, Andreas Journal of Biological Chemistry, Vol. 285, Issue 5 https://doi.org/10.1074/jbc.M109.081398	journal	November 2009
Bacterial species exhibit diversity in their mechanisms and capacity for protein disulfide bond formation Dutton, R. J.; Boyd, D.; Berkmen, M. Proceedings of the National Academy of Sciences, Vol. 105, Issue 33 https://doi.org/10.1073/pnas.0804621105	journal	August 2008
An Engineered Disulfide Bond between Residues 69 and 238 in Extended-Spectrum β-Lactamase Toho-1 Reduces Its Activity toward Third-Generation Cephalosporins ^‡ Shimizu-Ibuka, Akiko; Matsuzawa, Hiroshi; Sakai, Hiroshi Biochemistry, Vol. 43, Issue 50 https://doi.org/10.1021/bi048488u	journal	December 2004
Effect of disulfide-bond introduction on the activity and stability of the extended-spectrum class A β-lactamase Toho-1 Shimizu-Ibuka, Akiko; Matsuzawa, Hiroshi; Sakai, Hiroshi Biochimica et Biophysica Acta (BBA) - Proteins and Proteomics, Vol. 1764, Issue 8 https://doi.org/10.1016/j.bbapap.2006.06.004	journal	August 2006
The Class D β-lactamase family: residues governing the maintenance and diversity of function Szarecka, Agnieszka; Lesnock, Kimberly R.; Ramirez-Mondragon, Carlos A. Protein Engineering, Design and Selection, Vol. 24, Issue 10 https://doi.org/10.1093/protein/gzr041	journal	August 2011
General and condition-specific essential functions of Pseudomonas aeruginosa Lee, Samuel A.; Gallagher, Larry A.; Thongdee, Metawee Proceedings of the National Academy of Sciences, Vol. 112, Issue 16 https://doi.org/10.1073/pnas.1422186112	journal	April 2015
Phylogenetic Analysis of Burkholderia Species by Multilocus Sequence Analysis Estrada-de los Santos, Paulina; Vinuesa, Pablo; Martínez-Aguilar, Lourdes Current Microbiology, Vol. 67, Issue 1 https://doi.org/10.1007/s00284-013-0330-9	journal	February 2013
Legionella pneumophila adaptation to intracellular life and the host response: Clues from genomics and transcriptomics Jules, Matthieu; Buchrieser, Carmen FEBS Letters, Vol. 581, Issue 15 https://doi.org/10.1016/j.febslet.2007.05.026	journal	May 2007
The emerging diversity of Rickettsia Perlman, Steve J.; Hunter, Martha S.; Zchori-Fein, Einat Proceedings of the Royal Society B: Biological Sciences, Vol. 273, Issue 1598 https://doi.org/10.1098/rspb.2006.3541	journal	April 2006
β-Lactamases Medeiros, Antone A. British Medical Bulletin, Vol. 40, Issue 1 https://doi.org/10.1093/oxfordjournals.bmb.a071942	journal	January 1984
Comparison of -lactamases of classes A and D: 1.5-A crystallographic structure of the class D OXA-1 oxacillinase Sun, T. Protein Science, Vol. 12, Issue 1 https://doi.org/10.1110/ps.0224303	journal	January 2003
Structural Origins of Oxacillinase Specificity in Class D β-Lactamases June, Cynthia M.; Vallier, Beth C.; Bonomo, Robert A. Antimicrobial Agents and Chemotherapy, Vol. 58, Issue 1 https://doi.org/10.1128/AAC.01483-13	journal	October 2013
Inhibition of OXA-1 β-Lactamase by Penems Bethel, Christopher R.; Distler, Anne M.; Ruszczycky, Mark W. Antimicrobial Agents and Chemotherapy, Vol. 52, Issue 9 https://doi.org/10.1128/AAC.01677-07	journal	September 2008
Critical involvement of a carbamylated lysine in catalytic function of class D -lactamases Golemi, D.; Maveyraud, L.; Vakulenko, S. Proceedings of the National Academy of Sciences, Vol. 98, Issue 25 https://doi.org/10.1073/pnas.241442898	journal	November 2001
Backbone Dynamics of TEM-1 Determined by NMR: Evidence for a Highly Ordered Protein ^† Savard, Pierre-Yves; Gagné, Stéphane M. Biochemistry, Vol. 45, Issue 38 https://doi.org/10.1021/bi060414q	journal	September 2006
NMR Dynamics of PSE-4 β-Lactamase: An Interplay of ps-ns Order and μs-ms Motions in the Active Site Morin, Sébastien; Gagné, Stéphane M. Biophysical Journal, Vol. 96, Issue 11 https://doi.org/10.1016/j.bpj.2009.02.068	journal	June 2009
VMD: Visual molecular dynamics Humphrey, William; Dalke, Andrew; Schulten, Klaus Journal of Molecular Graphics, Vol. 14, Issue 1 https://doi.org/10.1016/0263-7855(96)00018-5	journal	February 1996
CHARMM: The biomolecular simulation program Brooks, B. R.; Brooks, C. L.; Mackerell, A. D. Journal of Computational Chemistry, Vol. 30, Issue 10 https://doi.org/10.1002/jcc.21287	journal	July 2009
Empirical force fields for biological macromolecules: Overview and issues Mackerell, Alexander D. Journal of Computational Chemistry, Vol. 25, Issue 13 https://doi.org/10.1002/jcc.20082	journal	January 2004
Comparison of simple potential functions for simulating liquid water Jorgensen, William L.; Chandrasekhar, Jayaraman; Madura, Jeffry D. The Journal of Chemical Physics, Vol. 79, Issue 2 https://doi.org/10.1063/1.445869	journal	July 1983
Particle mesh Ewald: An N ⋅log( N ) method for Ewald sums in large systems Darden, Tom; York, Darrin; Pedersen, Lee The Journal of Chemical Physics, Vol. 98, Issue 12 https://doi.org/10.1063/1.464397	journal	June 1993
Numerical integration of the cartesian equations of motion of a system with constraints: molecular dynamics of n-alkanes Ryckaert, Jean-Paul; Ciccotti, Giovanni; Berendsen, Herman J. C. Journal of Computational Physics, Vol. 23, Issue 3 https://doi.org/10.1016/0021-9991(77)90098-5	journal	March 1977
Accurate and efficient integration for molecular dynamics simulations at constant temperature and pressure Lippert, Ross A.; Predescu, Cristian; Ierardi, Douglas J. The Journal of Chemical Physics, Vol. 139, Issue 16 https://doi.org/10.1063/1.4825247	journal	October 2013
Constant pressure molecular dynamics algorithms Martyna, Glenn J.; Tobias, Douglas J.; Klein, Michael L. The Journal of Chemical Physics, Vol. 101, Issue 5 https://doi.org/10.1063/1.467468	journal	September 1994
A unified formulation of the constant temperature molecular dynamics methods Nosé, Shuichi The Journal of Chemical Physics, Vol. 81, Issue 1 https://doi.org/10.1063/1.447334	journal	July 1984
ProDy: Protein Dynamics Inferred from Theory and Experiments Bakan, A.; Meireles, L. M.; Bahar, I. Bioinformatics, Vol. 27, Issue 11, p. 1575-1577 https://doi.org/10.1093/bioinformatics/btr168	journal	April 2011
Dynamical networks in tRNA:protein complexes Sethi, A.; Eargle, J.; Black, A. A. Proceedings of the National Academy of Sciences, Vol. 106, Issue 16 https://doi.org/10.1073/pnas.0810961106	journal	April 2009
Experimental and computational determination of tRNA dynamics Alexander, Rebecca W.; Eargle, John; Luthey-Schulten, Zaida FEBS Letters, Vol. 584, Issue 2 https://doi.org/10.1016/j.febslet.2009.11.061	journal	November 2009
Exit Strategies for Charged tRNA from GluRS Black Pyrkosz, Alexis; Eargle, John; Sethi, Anurag Journal of Molecular Biology, Vol. 397, Issue 5 https://doi.org/10.1016/j.jmb.2010.02.003	journal	April 2010
Community structure in social and biological networks Girvan, M.; Newman, M. E. J. Proceedings of the National Academy of Sciences, Vol. 99, Issue 12 https://doi.org/10.1073/pnas.122653799	journal	June 2002
Residues crucial for maintaining short paths in network communication mediate signaling in proteins del Sol, Antonio; Fujihashi, Hirotomo; Amoros, Dolors Molecular Systems Biology, Vol. 2, Issue 1 https://doi.org/10.1038/msb4100063	journal	January 2006
Software news and updates carma: A molecular dynamics analysis program Glykos, Nicholas M. Journal of Computational Chemistry, Vol. 27, Issue 14 https://doi.org/10.1002/jcc.20482	journal	January 2006
NetworkView: 3D display and analysis of protein{middle dot}RNA interaction networks Eargle, J.; Luthey-Schulten, Z. Bioinformatics, Vol. 28, Issue 22 https://doi.org/10.1093/bioinformatics/bts546	journal	September 2012
A disulfide bridge near the active site of carbapenem-hydrolyzing class A β-lactamases might explain their unusual substrate profile Raquet, Xavier; Lamotte-Brasseur, Josette; Bouillenne, Fabrice Proteins: Structure, Function, and Genetics, Vol. 27, Issue 1 https://doi.org/10.1002/(SICI)1097-0134(199701)27:1<47::AID-PROT6>3.0.CO;2-K	journal	January 1997
Identification of OXA-23 carbapenemases: novel variant OXA-239 in Acinetobacter baumannii ST758 clinical isolates in Mexico Tamayo-Legorreta, E. M.; Garza-Ramos, U.; Barrios-Camacho, H. New Microbes and New Infections, Vol. 2, Issue 6 https://doi.org/10.1002/nmi2.60	journal	November 2014
Evolution to carbapenem-hydrolyzing activity in noncarbapenemase class D -lactamase OXA-10 by rational protein design De Luca, F.; Benvenuti, M.; Carboni, F. Proceedings of the National Academy of Sciences, Vol. 108, Issue 45 https://doi.org/10.1073/pnas.1110530108	journal	October 2011
Structures of the Class D Carbapenemases OXA-23 and OXA-146: Mechanistic Basis of Activity against Carbapenems, Extended-Spectrum Cephalosporins, and Aztreonam Kaitany, Kip-Chumba J.; Klinger, Neil V.; June, Cynthia M. Antimicrobial Agents and Chemotherapy, Vol. 57, Issue 10 https://doi.org/10.1128/AAC.00762-13	journal	July 2013
Common Clinical Substitutions Enhance the Carbapenemase Activity of OXA-51-Like Class D β-Lactamases from Acinetobacter spp. Mitchell, Joshua M.; Leonard, David A. Antimicrobial Agents and Chemotherapy, Vol. 58, Issue 11 https://doi.org/10.1128/AAC.03651-14	journal	August 2014
Are Current Molecular Dynamics Force Fields too Helical? Best, Robert B.; Buchete, Nicolae-Viorel; Hummer, Gerhard Biophysical Journal, Vol. 95, Issue 1 https://doi.org/10.1529/biophysj.108.132696	journal	July 2008
Force Field Bias in Protein Folding Simulations Freddolino, Peter L.; Park, Sanghyun; Roux, Benoît Biophysical Journal, Vol. 96, Issue 9 https://doi.org/10.1016/j.bpj.2009.02.033	journal	May 2009
The role of OXA-1 β-lactamase Asp66 in the stabilization of the active-site carbamate group and in substrate turnover Leonard, David A.; Hujer, Andrea M.; Smith, Brian A. Biochemical Journal, Vol. 410, Issue 3 https://doi.org/10.1042/BJ20070573	journal	February 2008
Critical Role of Tryptophan 154 for the Activity and Stability of Class D β-Lactamases ^, Baurin, Stéphane; Vercheval, Lionel; Bouillenne, Fabrice Biochemistry, Vol. 48, Issue 47 https://doi.org/10.1021/bi901548c	journal	November 2009
Crystal structure of the carbapenemase OXA-24 reveals insights into the mechanism of carbapenem hydrolysis Santillana, E.; Beceiro, A.; Bou, G. Proceedings of the National Academy of Sciences, Vol. 104, Issue 13 https://doi.org/10.1073/pnas.0607557104	journal	March 2007
Structural Basis for Enhancement of Carbapenemase Activity in the OXA-51 Family of Class D β-Lactamases Smith, Clyde A.; Antunes, Nuno Tiago; Stewart, Nichole K. ACS Chemical Biology, Vol. 10, Issue 8 https://doi.org/10.1021/acschembio.5b00090	journal	June 2015

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