Structural characterization of inhibitors with selectivity against members of a homologous enzyme family

Chemical Biology and Drug Design

Volumn 79, Issue 1, 2012, Pages 128-136

  Pavlovsky, Alexander G ^a   Liu, Xuying ^b   Faehnle, Christopher R ^c   Potente, Nina ^a   Viola, Ronald E ^a  

^a UNIVERSITY OF TOLEDO   (United States)

^b BETH ISRAEL DEACONESS MEDICAL CENTER   (United States)

^c Howard Hughes Medical Institute Cold Spring Harbor Laboratory Cold Spring Harbor   (United States)

Author keywords

Aspartate semialdehyde dehydrogenase; Enzyme inactivation; Enzyme inhibition; Structural studies; X ray crystallography

Indexed keywords

ASPARTATE SEMIALDEHYDE DEHYDROGENASE; ASPARTIC ACID; ENZYME INHIBITOR; ESSENTIAL AMINO ACID;

ARTICLE; ENZYME ACTIVE SITE; ENZYME ANALYSIS; ENZYME INACTIVATION; ENZYME INHIBITION; NONHUMAN; PRIORITY JOURNAL; STREPTOCOCCUS PNEUMONIAE; VIBRIO CHOLERAE;

ANTI-BACTERIAL AGENTS; ASPARTATE-SEMIALDEHYDE DEHYDROGENASE; BINDING SITES; CATALYTIC DOMAIN; COMPUTER SIMULATION; CRYSTALLOGRAPHY, X-RAY; DRUG DESIGN; ENZYME ACTIVATION; ENZYME INHIBITORS; PROPIONATES; STREPTOCOCCUS PNEUMONIAE; SUBSTRATE SPECIFICITY; VIBRIO CHOLERAE;

BACTERIA (MICROORGANISMS); STREPTOCOCCUS PNEUMONIAE; VIBRIO CHOLERAE;

EID: 84155164227     PISSN: 17470277     EISSN: 17470285     Source Type: Journal    
DOI: 10.1111/j.1747-0285.2011.01267.x     Document Type: Article

References (26)

1. Cohen G.N. (1983) The common pathway to lysine, methionine, and threonine. In: Herrmann K.M., Somerville R.L., editors. Amino Acids: Biosynthesis and Genetic Regulation. Reading, MA: Addison-Wesley; p. 147-171.
2. Viola R.E. (2001) The central enzymes of the aspartate family of amino acid biosynthesis. Accounts Chem Res;34:339-349.
3. 2+-dipicolinate. J Bacteriol;185:2315-2329.
4. Van Heijenoort J. (2001) Recent advances in the formation of the bacterial peptidoglycan monomer unit. Nat Prod Reports;18:503-519.
5. Lyon G.J., Novick R.P. (2004) Peptide signaling in Staphylococcus aureus and other Gram-positive bacteria. Peptides;25:1389-1403.
6. Chen X., Schauder S., Potier N., Van Dorsselaer A., Pelczer I., Bassler B.L., Highson F.M. (2002) Structural identification of a bacterial quorum-sensing signal containing boron. Nature;415:545-549.
7. Galan J.E., Nakayama K., Curtiss R. (1990) Cloning and characterization of the asd gene of Salmonella typhimurium: use in stable maintenance of recombinant plasmids in Salmonella vaccine strains. Gene;94:29-35.
8. Gerdes S.Y., Scholle M.D., Campbell J.W., Balazsi G., Ravasz E., Daugherty M.D., Somera A.L. et al. (2003) Experimental determination and system level analysis of essential genes in Escherichia coli MG1655. J Bacteriol;185:5673-5684.
9. Kobayashi K., Ehrlich S.D., Albertini A., Amati, G., Andersen, K.K., Amaud, M., Asai, K. et al. (2003) Essential Bacillus subtilis genes. Proc Natl Acad Sci USA;100:4678-4683.
10. Salama N.R., Shepard B., Falkow S. (2004) Global transposon mutagenesis and essential gene analysis of Helicobacter pylori. J Bacteriol;186:7926-7935.
11. Becker D., Selbach M., Rollenhagen C., Ballmaier M., Meyer T.F., Mann M., Bumann D. (2006) Robust Salmonella metabolism limits possibilities for new antimicrobials. Nature;440:303-307.
12. Carr R., Jhoti H. (2002) Structure-based screening of low-affinity compounds. Drug Discov Today;7:522-527.
13. Hopkins A.L., Groom C.R., Alex A. (2004) Ligand efficiency: a useful metric for lead selection. Drug Discov Today;9:430-431.
14. Gao G., Liu X., Pavlovsky A., Viola R.E. (2010) Identification of selective enzyme inhibitors by fragment library screening. J Biomol Screen;15:1042-1050.
15. Otwinowski Z., Minor W. (1997) Processing of X-ray diffraction data collected in oscillation mode. Methods Enzymol;276:307-326.
16. Collaborative Computational Project (1994) The CCP4 suite: programs for protein crystallography. Acta Cryst;D50:760-763.
17. Winn M.D., Isupov M.N., Murshudov G.N. (2001) Use of TLS parameters to model anisotropic displacements in macromolecular refinement. Acta Cryst;D57:122-133.
18. Emsley P., Cowtan K. (2004) Coot: model-building tools for molecular graphics. Acta Cryst;D60:2126-2132.
19. Schuttelkopf A.W., van Aalten D.M.F. (2004) PRODRG: a tool for high-throughput crystallography of protein-ligand complexes. Acta Cryst;D60:1355-1363.
20. Cox R.J., Gibson J.S., Martin M.B. (2002) Aspartyl phosphonates and phosphoramidates: the first synthetic inhibitors of bacterial aspartate-semialdehyde dehydrogenase. ChemBioChem;3:874-886.
21. Han S., Moore R.A., Viola R.E. (2003) A facile synthesis of a difluoromethylene analog of β-aspartyl phosphate as an inhibitor of l-aspartate-β-semialdehyde dehydrogenase. Synlett;2003:845-846.
22. Faehnle C.R., Liu X., Le Coq J., Viola R.E. (2006) An examination of key intermediates in the catalytic cycle of aspartate semialdehyde dehydrogenase from a gram-positive bacteria. J Biol Chem;281:31031-31040.
23. Faehnle C.R., Blanco J., Viola R.E. (2004) Structural basis for discrimination between oxyanion substrate or inhibitors in aspartate-β-semialdehyde dehydrogenase. Acta Cryst;D60:2320-2324.
24. Blanco J., Moore R.A., Kalabeeswaran V., Viola R.E. (2003) A structural basis for the mechanism of aspartate-β-semialdehyde dehydrogenase from Vibrio cholerae. Protein Sci;12:27-33.
25. Blanco J., Moore R.A., Faehnle C.R., Coe D.M., Viola R.E. (2004) The role of substrate-binding groups in the mechanism of aspartate-β-semialdehyde dehydrogenase. Acta Cryst;D60:1388-1395.
26. Blanco J., Moore R.A., Viola R.E. (2003) Capture of an intermediate in the catalytic cycle of l-aspartate-β-semialdehyde dehydrogenase. Proc Natl Acad Sci USA;100:12613-12617.