Function of the D -alanine: D -alanine ligase lid loop: A molecular modeling and bioactivity study

Journal of Medicinal Chemistry

Volumn 55, Issue 15, 2012, Pages 6849-6856

  Hrast, Martina ^a   Vehar, Blaž ^b   Turk, Samo ^a   Konc, Janez ^b   Gobec, Stanislav ^a   Janežič, Dušanka ^b  

^a UNIVERSITY OF LJUBLJANA   (Slovenia)

^b NATIONAL INSTITUTE OF CHEMISTRY   (Slovenia)

Author keywords

[No Author keywords available]

Indexed keywords

2 [(7 METHOXY 4 METHYLQUINAZOLIN 2 YL)AMINO]PYRIMIDINE 4,6 DIOL; 2,4 DIKETO 5 (PHENYLCARBAMOYL) 1H PYRIMIDIN 6 OLATE; 4 [(ISONICOTINOYLHYDRAZONO)METHYL] 6 KETO 1H PYRIMIDIN 2 OLATE; ADENOSINE TRIPHOSPHATE; CYCLOSERINE; DEXTRO ALANINE DEXTRO ALANINE LIGASE; ENZYME INHIBITOR; N' [(2,1,3 BENZOTHIADIAZOL 5 YLCARBONYL)OXY] 1,2,4 OXADIAZOLE 3 CARBOXIMIDAMIDE; N' [[(3 CHLOROANILINO)CARBONYL]OXY]ISOXAZOLE 5 CARBOXIMIDAMIDE; N' [[(4 CHLOROANILINO)CARBONYL]OXY]ISOXAZOLE 5 CARBOXIMIDAMIDE; N' [[(4 CHLOROANILINO)CARBONYL]OXY]PYRAZINE 2 CARBOXIMIDAMIDE; PEPTIDOGLYCAN; STK 046256; UNCLASSIFIED DRUG; ZINC 01868219; ZINC 04351284; ZINC 05092259; ZINC 08536193; ZINC 1586033; ZINC 18142224;

ARTICLE; BINDING SITE; ENZYME CONFORMATION; ENZYME INHIBITION; ENZYME STRUCTURE; ESCHERICHIA COLI; MOLECULAR DYNAMICS; MOLECULAR MODEL; NONHUMAN; PROTEIN FUNCTION; PROTEIN SYNTHESIS; SALMONELLA TYPHIMURIUM;

BACTERIAL PROTEINS; BENZOTHIAZOLES; ENZYME ASSAYS; ESCHERICHIA COLI PROTEINS; ISOXAZOLES; MOLECULAR DYNAMICS SIMULATION; PEPTIDE SYNTHASES; PROTEIN BINDING; PROTEIN CONFORMATION; PYRAZINES; PYRIMIDINES; STEREOISOMERISM; STRUCTURE-ACTIVITY RELATIONSHIP; THERMUS;

EID: 84864950132     PISSN: 00222623     EISSN: 15204804     Source Type: Journal    
DOI: 10.1021/jm3006965     Document Type: Article

References (46)

1. Barreteau, H.; Kovac, A.; Boniface, A.; Sova, M.; Gobec, S.; Blanot, D. Cytoplasmic steps of peptidoglycan biosynthesis FEMS Microbiol. Rev. 2008, 32, 168-207
2. Walsh, C. T. Enzymes in the d -alanine branch of bacterial-cell wall peptidoglycan assembly J. Biol. Chem. 1989, 264, 2393-2396
3. Kahan, F. M.; Kahan, J. S.; Cassidy, P. J.; Kropp, H. Mechanism of action of fosfomycin (phosphonomycin) Ann. N.Y. Acad. Sci. 1974, 235, 364-386
4. Vollmer, W.; Blanot, D.; de Pedro, M. A. Peptidoglycan structure and architecture FEMS Microbiol. Rev. 2008, 32, 149-167
5. Ellsworth, B. A.; Tom, N. J.; Bartlett, P. A. Synthesis and evaluation of inhibitors of bacterial d -alanine: d -alanine ligases Chem. Biol. 1996, 3, 37-44
6. Neuhaus, F. C.; Lynch, J. L. The enzymatic synthesis of d -alanyl- d -alanine. 3. On the inhibition of d -Alanyl- d -Alanine synthetase by the antibiotic d -cycloserine Biochemistry 1964, 3, 471-480
7. Lambert, M. P.; Neuhaus, F. C. Mechanism of d -cycloserine action: alanine racemase from Escherichia coli W J. Bacteriol. 1972, 110, 978-987
8. WHO. Treatment of Tuberculosis: Guidelines, 4 th ed.; World Health Organization: Geneva, Switzerland, 2010; pp 84-85.
9. Zawadzke, L. E.; Bugg, T. D. H.; Walsh, C. T. Existence of 2 d -alanine- d -alanine ligases in Escherichia coli. Cloning and sequencing of the DdlA gene and purification and characterization of the DdlA and DdlB enzymes Biochemistry 1991, 30, 1673-1682
10. Daub, E.; Zawadzke, L. E.; Botstein, D.; Walsh, C. T. Isolation, cloning, and sequencing of the Salmonella typhimurium DdlA gene with purification and characterization of its product, d -alanine- d -alanine ligase (ADP forming) Biochemistry 1988, 27, 3701-3708
11. Galperin, M. Y.; Koonin, E. V. A diverse superfamily of enzymes with ATP-dependent carboxylate-amine/thiol ligase activity Protein Sci. 1997, 6, 2639-2643
12. Fan, C.; Park, I. S.; Walsh, C. T.; Knox, J. R. d -Alanine: d -alanine ligase: phosphonate and phosphinate intermediates with wild type and the Y216F mutant Biochemistry 1997, 36, 2531-2538
13. Shi, Y.; Walsh, C. T. Active-site mapping of Escherichia coli d -Ala- d -Ala ligase by structure-based mutagenesis Biochemistry 1995, 34, 2768-2776
14. Lee, J. H.; Na, Y.; Song, H. E.; Kim, D.; Park, B. H.; Rho, S. H.; Im, Y. J.; Kim, M. K.; Kang, G. B.; Lee, D. S.; Eom, S. H. Crystal structure of the apo form of d -alanine: d -alanine ligase (Ddl) from Thermus caldophilus: a basis for the substrate-induced conformational changes Proteins 2006, 64, 1078-1082
15. Tytgat, I.; Colacino, E.; Tulkens, P. M.; Poupaert, J. H.; Prevost, M.; Van Bambeke, F. dd- Ligases as a potential target for antibiotics: past, present and future Curr. Med. Chem. 2009, 16, 2566-2580
16. Richards, F. M.; Kundrot, C. E. Identification of structural motifs from protein coordinate data: secondary structure and first-level supersecondary structure Proteins 1988, 3, 71-84
17. Kitamura, Y.; Ebihara, A.; Agari, Y.; Shinkai, A.; Hirotsu, K.; Kuramitsu, S. Structure of d -alanine- d -alanine ligase from Thermus thermophilus HB8: cumulative conformational change and enzyme-ligand interactions Acta Crystallogr. D 2009, 65, 1098-1106
18. Kovac, A.; Konc, J.; Vehar, B.; Bostock, J. M.; Chopra, I.; Janezic, D.; Gobec, S. Discovery of new inhibitors of d -alanine: d -alanine ligase by structure-based virtual screening J. Med. Chem. 2008, 51, 7442-7448
19. Vehar, B.; Hrast, M.; Kovac, A.; Konc, J.; Mariner, K.; Chopra, I.; ONeill, A.; Janezic, D.; Gobec, S. Ellipticines and 9-acridinylamines as inhibitors of d -alanine: d -alanine ligase Bioorg. Med. Chem. 2011, 19, 5137-5146
20. Guido, R. V.; Oliva, G.; Andricopulo, A. D. Virtual screening and its integration with modern drug design technologies Curr. Med. Chem. 2008, 15, 37-46
21. Brooks, B. R.; Brooks, C. L., 3rd; Mackerell, A. D., Jr.; Nilsson, L.; Petrella, R. J.; Roux, B.; Won, Y.; Archontis, G.; Bartels, C.; Boresch, S.; Caflisch, A.; Caves, L.; Cui, Q.; Dinner, A. R.; Feig, M.; Fischer, S.; Gao, J.; Hodoscek, M.; Im, W.; Kuczera, K.; Lazaridis, T.; Ma, J.; Ovchinnikov, V.; Paci, E.; Pastor, R. W.; Post, C. B.; Pu, J. Z.; Schaefer, M.; Tidor, B.; Venable, R. M.; Woodcock, H. L.; Wu, X.; Yang, W.; York, D. M.; Karplus, M. CHARMM: the biomolecular simulation program J. Comput. Chem. 2009, 30, 1545-1614
22. Schlitter, J.; Engels, M.; Kruger, P.; Jacoby, E.; Wollmer, A. Targeted molecular-dynamics simulation of conformational change. Application to the Tâ†"R transition in insulin Mol. Simul. 1993, 10, 291-308
23. Woodcock, H. L.; Hodoscek, M.; Sherwood, P.; Lee, Y. S.; Schaefer, H. F.; Brooks, B. R. Exploring the quantum mechanical/molecular mechanical replica path method: a pathway optimization of the chorismate to prephenate Claisen rearrangement catalyzed by chorismate mutase Theor. Chem. Acc. 2003, 109, 140-148
24. Chu, J. W.; Trout, B. L.; Brooks, B. R. A super-linear minimization scheme for the nudged elastic band method J. Chem. Phys. 2003, 119, 12708-12717
25. Perdih, A.; Solmajer, T. MurD ligase from Escherichia coli: C-terminal domain closing motion Comput. Theor. Chem. 2012, 979, 73-81
26. Czerminski, R.; Elber, R. Reaction-path study of conformational transitions in flexible systems. Applications to peptides J. Chem. Phys. 1990, 92, 5580-5601
27. Irwin, J. J.; Shoichet, B. K. ZINC: a free database of commercially available compounds for virtual screening J. Chem. Inf. Model. 2005, 45, 177-182
28. Rarey, M.; Kramer, B.; Lengauer, T.; Klebe, G. A fast flexible docking method using an incremental construction algorithm J. Mol. Biol. 1996, 261, 470-489
29. Swann, S. L.; Brown, S. P.; Muchmore, S. W.; Patel, H.; Merta, P.; Locklear, J.; Hajduk, P. J. A unified, probabilistic framework for structure- and ligand-based virtual screening J. Med. Chem. 2011, 54, 1223-1232
30. Kovac, A.; Majce, V.; Lenarsic, R.; Bombek, S.; Bostock, J. M.; Chopra, I.; Polanc, S.; Gobec, S. Diazenedicarboxamides as inhibitors of d -alanine- d -alanine ligase (Ddl) Bioorg. Med. Chem. Lett. 2007, 17, 2047-2054
31. Borstnik, U.; Hodoscek, M.; Janezic, D. Improving the performance of molecular dynamics simulations on parallel clusters J. Chem. Inf. Comput. Sci. 2004, 44, 359-364
32. Borstnik, U.; Janezic, D. Symplectic molecular dynamics simulations on specially designed parallel computers J. Chem. Inf. Model. 2005, 45, 1600-1604
33. Eswar, N.; Webb, B.; Marti-Renom, M. A.; Madhusudhan, M. S.; Eramian, D.; Shen, M. Y.; Pieper, U.; Sali, A. Comparative Protein Structure Modeling Using Modeller. In Current Protocols in Bioinformatics; Wiley: New York, 2006; Chapter 5, Unit 5.6.
34. Berman, H. M.; Westbrook, J.; Feng, Z.; Gilliland, G.; Bhat, T. N.; Weissig, H.; Shindyalov, I. N.; Bourne, P. E. The Protein Data Bank Nucleic Acids Res. 2000, 28, 235-242; www.pdb.org
35. Feller, S. E.; MacKerell, A. D. An improved empirical potential energy function for molecular simulations of phospholipids J. Phys. Chem. B 2000, 104, 7510-7515
36. Ryckaert, J. P.; Ciccotti, G.; Berendsen, H. J. C. Numerical-integration of Cartesian equations of motion of a system with constraints. Molecular-dynamics of n -alkanes J. Comput. Phys. 1977, 23, 327-341
37. Batcho, P. F.; Case, D. A.; Schlick, T. Optimized particle-mesh Ewald/multiple-time step integration for molecular dynamics simulations J. Chem. Phys. 2001, 115, 4003-4018
38. 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 Cambridge Structural Database J. Chem. Inf. Model. 2010, 50, 572-584
39. de Hoon, M. J. L.; Imoto, S.; Nolan, J.; Miyano, S. Open source clustering software Bioinformatics 2004, 20, 1453-1454
40. Pavlov, D.; Rybalkin, M.; Karulin, B.; Kozhevnikov, M.; Savelyev, A.; Churinov, A. Indigo: universal cheminformatics API J. Cheminf. 2011, 3 (Suppl. 1) P4
41. Willett, P.; Barnard, J. M.; Downs, G. M. Chemical similarity searching J. Chem. Inf. Comput. Sci. 1998, 38, 983-996
42. Oliphant, T. E. Python for scientific computing Comput. Sci. Eng. 2007, 9, 10-20
43. Humphrey, W.; Dalke, A.; Schulten, K. VMD: visual molecular dynamics J. Mol. Graphics 1996, 14, 33-38
44. Williams, T.; Keeley, C. Gnuplot 4.4: An Interactive Plotting Program. http://gnuplot.sourceforge.net (accessed Sep 2011).
45. Walsh, A. W.; Falk, P. J.; Thanassi, J.; Discotto, L.; Pucci, M. J.; Ho, H. T. Comparison of the d -glutamate-adding enzymes from selected gram-positive and gram-negative bacteria J. Bacteriol. 1999, 181, 5395-5401
46. McGovern, S. L.; Helfand, B. T.; Feng, B.; Shoichet, B. K. A specific mechanism of nonspecific inhibition J. Med. Chem. 2003, 46, 4265-4272