Inhibitor design strategy based on an enzyme structural flexibility: A case of bacterial MurD ligase

Journal of Chemical Information and Modeling

Volumn 54, Issue 5, 2014, Pages 1451-1466

  Perdih, Andrej ^a,b   Hrast, Martina ^c   Barreteau, Hélène ^d   Gobec, Stanislav ^c   Wolber, Gerhard ^b   Solmajer, Tom ^a  

^a NATIONAL INSTITUTE OF CHEMISTRY   (Slovenia)

^b FREIE UNIVERSITÄT BERLIN   (Germany)

^c UNIVERSITY OF LJUBLJANA   (Slovenia)

^d INSTITUTE FOR INTEGRATIVE BIOLOGY OF THE CELL I2BC   (France)

Author keywords

[No Author keywords available]

Indexed keywords

BIOCHEMISTRY; COMPUTATIONAL CHEMISTRY; MOLECULAR DYNAMICS; STRUCTURAL DESIGN;

ANTIBACTERIAL DRUG DESIGN; BACTERIAL PEPTIDOGLYCAN; CLASSICAL MOLECULAR DYNAMICS; COMPUTATIONAL STUDIES; DRUG DESIGN STRATEGIES; DRUG DISCOVERY PROCESS; STRUCTURAL FLEXIBILITIES; TARGETED MOLECULAR DYNAMICS;

ENZYME INHIBITION;

ADENOSINE TRIPHOSPHATE; ENZYME INHIBITOR; PEPTIDE SYNTHASE; THIAZOLE DERIVATIVE; UDP-N-ACETYLMURAMOYLALANINE-D-GLUTAMATE LIGASE;

ANTAGONISTS AND INHIBITORS; CHEMISTRY; COMPUTER INTERFACE; DRUG DESIGN; DRUG SCREENING; ENZYMOLOGY; ESCHERICHIA COLI; METABOLISM; MOLECULAR DOCKING; MOLECULAR DYNAMICS; PROTEIN CONFORMATION;

ADENOSINE TRIPHOSPHATE; DRUG DESIGN; DRUG EVALUATION, PRECLINICAL; ENZYME INHIBITORS; ESCHERICHIA COLI; MOLECULAR DOCKING SIMULATION; MOLECULAR DYNAMICS SIMULATION; PEPTIDE SYNTHASES; PROTEIN CONFORMATION; THIAZOLES; USER-COMPUTER INTERFACE;

EID: 84901599414     PISSN: 15499596     EISSN: 1549960X     Source Type: Journal    
DOI: 10.1021/ci500104m     Document Type: Article

References (51)

1. Silver, L. L. Does the cell wall of bacteria remain a viable source of targets for novel antibiotics? Biochem. Pharmacol. 2006, 71, 996-1005
2. Brown, E. D.; Wright, G. D. New Targets and Screening Approaches in Antimicrobial Drug Discovery Chem. Rev. 2005, 105, 759-774
3. Silver, L. L. Challenges of Antibacterial Discovery Clin. Microbiol. Rev. 2011, 24, 71-109
4. Vollmer, W.; Blanot, D.; de Pedro, M. A. Peptidoglycan structure and architecture FEMS Microbiol. Rev. 2008, 32, 149-167
5. Barreteau, H.; Kovač, A.; Boniface, A.; Sova, M.; Gobec, S.; Blanot, D. FEMS Microbiol. Rev. 2008, 32, 168-207
6. Sink, R.; Barreteau, H.; Patin, D.; Mengin-Lecreulx, D.; Gobec, S.; Blanot, D. BioMol. Concepts 2013, 4, 539-546
7. van Heijenoort, J. Recent advances in the formation of the bacterial peptidoglycan monomer unit Nat. Prod. Rep. 2001, 18, 503-519
8. Smith, C. S. Structure, Function and Dynamics in the mur Family of Bacterial Cell Wall Ligases J. Mol. Biol. 2006, 362, 640-655
9. Bertrand, J. A.; Auger, G.; Martin, L.; Fanchon, E.; Blanot, D.; Le Beller, D.; van Heijenoort, J.; Dideberg, O. Determination of the MurD mechanism through crystallographic analysis of enzyme complexes J. Mol. Biol. 1999, 289, 579-590
10. Perdih, A.; Hodoscek, M.; Solmajer, T. MurD ligase from E. coli: Tetrahedral intermediate formation study by hybrid quantum mechanical/molecular mechanical replica path method Proteins 2009, 74, 744-7599
11. Anderson, M. S.; Eveland, S. S.; Onishi, H.; Pompliano, D. L. Kinetic mechanism of the Escherichia coli UDPMurNAc-tripeptide D-alanyl-D-alanine-adding enzyme: use of a glutathione S-transferase fusion Biochemistry 1996, 35, 16264-16269
12. Emanuele, J. J., Jr.; Jin, H.; Yanchunas, J., Jr.; Villafranca, J. J. Evaluation of the kinetic mechanism of Escherichia coli uridine diphosphate-N-acetylmuramate:L-alanine ligase Biochemistry 1997, 36, 7264-7271
13. Bouhss, A.; Dementin, S.; van Heijenoort, J.; Parquet, C.; Blanot, D. MurC and MurD synthetases of peptidoglycan biosynthesis: Borohydride trapping of acyl-phosphate intermediates Methods Enzymol. 2002, 354, 189-196
14. Bertrand, J. A.; Fanchon, E.; Martin, L.; Chantalat, L.; Auger, G.; Blanot, D.; van Heijenoort, J.; Dideberg, O. "Open" structures of MurD: domain movements and structural similarities with folylpolyglutamate synthetase J. Mol. Biol. 2000, 301, 1257-1266
15. Perdih, A.; Kotnik, M.; Hodoscek, M.; Solmajer, T. Targeted Molecular Dynamics Simulation Studies of Binding and Conformational Changes in E.Coli MurD Proteins 2007, 68, 243-254
16. Perdih, A.; Solmajer, T. MurD ligase from E.coli: C-terminal domain closing motion Comput. Theor. Chem. 2012, 979, 73-81
17. Zoeiby, A. E.; Sanschagrin, F.; Levesque, R. C. Structure and function of the Mur enzymes: Development of novel Inhibitors Mol. Microbiol. 2002, 47, 1-12
18. Perdih, A.; Kovač, A.; Wolber, G.; Blanot, D.; Gobec, S.; Solmajer, T. Discovery of novel benzene 1,3-dicarboxylic acid inhibitors of bacterial MurD and MurE ligases by structure-based virtual screening approach Bioorg. Med. Chem. Lett. 2009, 19, 2668-2673
19. Tanner, M. E.; Vaganay, S.; van Heijenoort, J.; Blanot, D. Phosphinate Inhibitors of the D-Glutamic Acid-Adding Enzyme of Peptidoglycan Biosynthesis J. Org. Chem. 1996, 61, 1756-1760
20. Kotnik, M.; Humljan, J.; Contreras-Martel, C.; Oblak, M.; Kristan, K.; Hervé, M.; Blanot, D.; Urleb, U.; Gobec, S.; Dessen, A.; Solmajer, T. Structural and Functional Characterization of Enantiomeric Glutamic Acid Derivatives as Potential Transition State Analogue Inhibitors of MurD Ligase J. Mol. Biol. 2007, 370, 107-115
21. Perdih, A.; Bren, U.; Solmajer, T. Binding Free-Energy Calculations of N -Sulfonyl Glutamic Acid Inhibitors of MurD Ligase J. Mol. Model. 2009, 15, 983-996
22. Perdih, A.; Wolber, G.; Solmajer, T. Molecular dynamics simulation and linear interaction energy study of D-Glu-based inhibitors of the MurD ligase J. Comput.-Aided Mol. Des. 2013, 27, 723-738
23. Tomašić, T.; Kovač, A.; Klebe, G.; Blanot, D.; Gobec, S.; Kikelj, D.; Mašič, L. P. Virtual screening for potential inhibitors of bacterial MurC and MurD ligases J. Mol. Model. 2012, 18, 1063-1072
24. Šink, R.; Kovač, A.; Tomasić, T.; Rupnik, V.; Boniface, A.; Bostock, J.; Chopra, I.; Blanot, D.; Masic, L. P.; Gobec, S.; Zega, A. Synthesis and biological evaluation of N-acylhydrazones as inhibitors of MurC and MurD ligases ChemMedChem. 2008, 9, 1362-1370
25. Carlson, H. A. Protein flexibility and drug design: how to hit a moving target Curr. Opin. Chem. Biol. 2002, 4, 447-452
26. Teague, S. J. Implications of protein flexibility for drug discovery Nat. Rev. Drug Discovery 2003, 2, 527-541
27. Knegtel, R. M.; Kuntz, I. D.; Oshiro, C. M. Molecular docking to ensembles of protein structures J. Mol. Biol. 1997, 266, 424-440
28. Meagher, K. L.; Carlson, H. A. Incorporating protein flexibility in structure-based drug discovery: using HIV-1 protease as a test case J. Am. Chem. Soc. 2004, 126, 13276-13281
29. Kunze, J.; Todoroff, T.; Schneider, P.; Rodrigues, T.; Geppert, T.; Reisen, F.; Schreuder, H.; Saas, J.; Hessler, G.; Baringhaus, K.-G.; Schneider, G. Targeting Dynamic Pockets of HIV-1 Protease by Structure-Based Computational Screening for Allosteric Inhibitors J. Chem. Inf. Model. 2014, 54, 987-991
30. Longenecker, K. L.; Stamper, G. F.; Hajduk, P. J.; Fry, E. H.; Jakob, C. G.; Harlan, J. E.; Edalji, R.; Bartley, D. M.; Walter, K. A.; Solomon, L. R.; Holzman, T. F.; Gu, Y. G.; Lerner, C. G.; Beutel, B. A.; Stoll, V. S. Structure of MurF from Streptococcus pneumoniae co-crystallized with a small molecule inhibitor exhibits interdomain closure Protein Sci. 2005, 14, 3039-3047
31. Goodford, P. J. A computational procedure for determining energetically favorable binding sites on biologically important macromolecules J. Med. Chem. 1985, 28, 857-864
32. Ortuso, F.; Langer, T.; Alcaro, S. GBPM: GRID-based pharmacophore model: concept and application studies to protein-protein recognition Bioinformatics. 2006, 22, 1449-1455
33. Wolber, G.; Langer, T. LigandScout: 3-D Pharmacophores Derived from Protein-Bound Ligands and Their Use as Virtual Screening Filters J. Chem. Inf. Model. 2005, 45, 160-169
34. Wolber, G.; Dornhofer, A.; Langer, T. Efficient overlay of small organic molecules using 3D pharmacophores J. Comput.-Aided Mol. Des. 2006, 20, 773-788
35. Jones, G.; Willett, P.; Glen, R. C.; Leach, A. R.; Taylor, R. Development and validation of a genetic algorithm for flexible docking J. Mol. Biol. 1997, 267, 727-748
36. Kirchmair, J.; Markt, P.; Distinto, S.; Wolber, G.; Langer, T. Evaluation of the performance of 3D virtual screening protocols: RMSD comparisons, enrichment assessments, and decoy selection-what can we learn from earlier mistakes? J. Comput.-Aided Mol. Des. 2008, 22, 213-228
37. McGovern, S. L.; Stoichet, B. K. Kinase inhibitors: not just for kinases anymore J. Med. Chem. 2003, 46, 1478-1483
38. Brvar, M.; Perdih, A.; Oblak, M.; Peterlin Masic, L.; Solmajer, T. In silico discovery of 2-amino-4-(2,4-dihydroxyphenyl)thiazoles as novel inhibitors of DNA gyrase B Bioorg. Med. Chem. Lett. 2010, 20, 958-962
39. Brooks, B. R.; Bruccoleri, R. E.; Olafson, B. D.; States, D. J.; Swaminathen, S.; Karplus, M. CHARMM: A Program for Macromolecular Energy, Minimization, and Dynamics Calculations J. Comput. Chem. 1983, 4, 187-217
40. Jo, S.; Kim, T.; Iyer, V. G.; Im, W. CHARMM-GUI: A web-based graphical user interface for CHARMM J. Comput. Chem. 2008, 29, 1859-1865
41. Šink, R.; Kotnik, M.; Barreteau, H.; Zega, A.; Gobec, S.; Blanot, D.; Dessen, A.; Contreras-Martel, C. Conformational insights into a rigid body C-terminal domain movement of MurD ligase Drugs Future 2010, 35 (Suplement A) PC257, 170
42. OMEGA 2.4.6; OpenEye Scientific Software, Inc.: Santa Fe, NM, http://www.eyesopen.com.
43. Hawkins, P. C. D.; Skillman, A. G.; Warren, G. L.; Ellingson, B. A.; Stahl, M. T. Conformer generation with OMEGA: Algorithm and validation using high quality structures from the protein databank and the Cambridge structural database J. Chem. Inf. Model. 2010, 50, 572-584
44. Auger, G.; Martin, L.; Bertrand, J.; Ferrari, P.; Fanchon, E.; Vaganay, S.; Petillot, Y.; van Heijenoort, J.; Blanot, D.; Dideberg, O. Large-scale preparation, purification, and crystallization of UDP-N-acetylmuramoyl-L- alanine: D-glutamate ligase from Escherichia coli Prot. Express Purif. 1998, 13, 23-29
45. Lanzetta, P. A.; Alvarez, L. J.; Reinach, P. S.; Candia, O. An improved assay for nanomole amounts of inorganic phosphate Anal. Biochem. 1979, 100, 95-97
46. MacKerell, A. D., Jr.; Bashford, D.; Bellott, M.; Dunbrack, R. L., Jr.; Evanseck, J. D.; Field, M. J.; Fischer, S.; Gao, J.; Guo, H.; Ha, S.; Joseph-McCarthy, D.; Kuchnir, L.; Kuczera, K.; Lau, F. T. K; Mattos, C.; Michnick, S.; Ngo, T.; Nguyen, D. T.; Prodhom, B.; Reiher, W. E., III; Roux, B.; Schlenkrich, M.; Smith, J. C.; Stote, R.; Straub, J.; Watanabe, M.; Wiorkiewicz-Kuczera, J.; Yin, D.; Karplus, M. All-atom empirical potential for molecular modeling and dynamics Studies of proteins J. Phys. Chem. B 1998, 102, 3586-3616
47. MacKerell, A. D., Jr.; Feig, M.; Brooks, C. L., III. Extending the treatment of backbone energetics in protein force fields: limitations of gas-phase quantum mechanics in reproducing protein conformational distributions in molecular dynamics simulations J. Comput. Chem. 2004, 25, 1400-1415
48. Vanommeslaeghe, K.; Hatcher, E.; Acharya, C.; Kundu, S.; Zhong, S.; Shim, J.; Darian, E.; Guvench, O.; Lopes, P.; Vorobyov, I.; Mackerell, A. D., Jr. CHARMM general force field: A force field for drug-like molecules compatible with the CHARMM all-atom additive biological force fields J. Comput. Chem. 2010, 671-690
49. Jorgensen, W. L.; Chandrasekhar, J.; Madura, J. D.; Impey, R. W.; Klein, M. L. Comparison of simple potential functions for simulating liquid water J. Chem. Phys. 1983, 79, 926-935
50. Humphrey, W.; Dalke, A.; Schulten, K. VMD: visual molecular dynamics J. Mol. Graphics 1996, 14, 33-38
51. Frishman, D.; Argos, P. Knowledge-based protein secondary structure assignment Proteins 1995, 23, 566-579