Glutamate racemase is the primary target of β-chloro-D-alanine in Mycobacterium tuberculosis

Antimicrobial Agents and Chemotherapy

Volumn 60, Issue 10, 2016, Pages 6091-6099

  Prosser, Gareth A ^a,b   Rodenburg, Anne ^a   Khoury, Hania ^a   De Chiara, Cesira ^a   Howell, Steve ^a   Snijders, Ambrosius P ^a   De Carvalho, Luiz Pedro S ^a  

^a THE FRANCIS CRICK INSTITUTE   (United Kingdom)

^b NATIONAL INSTITUTE OF ALLERGY AND INFECTIOUS DISEASES   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

ALANINE RACEMASE; ANTIINFECTIVE AGENT; BETA CHLORO DEXTRO ALANINE; CYCLOSERINE; DEXTRO ALANINE; DEXTRO GLUTAMIC ACID; GLUTAMATE RACEMASE; ISOMERASE; PEPTIDOGLYCAN; TUBERCULOSTATIC AGENT; UNCLASSIFIED DRUG; 3-CHLOROALANINE; BACTERIAL PROTEIN; BETA ALANINE; ENZYME INHIBITOR; PROTEIN BINDING; RECOMBINANT PROTEIN;

ANTIBACTERIAL ACTIVITY; ANTIMICROBIAL ACTIVITY; ARTICLE; BACTERIAL STRAIN; BIOSYNTHESIS; CONCENTRATION RESPONSE; CONTROLLED STUDY; DRUG EFFECT; DRUG MECHANISM; DRUG POTENCY; DRUG TARGETING; ENZYME INACTIVATION; ENZYME INHIBITION; ENZYMOLOGY; IN VITRO STUDY; IN VIVO STUDY; METABOLOMICS; MICROBIOLOGY; MYCOBACTERIUM TUBERCULOSIS; NONHUMAN; PRIORITY JOURNAL; PROTEOMICS; WHOLE CELL; AMINO ACID SEQUENCE; ANALOGS AND DERIVATIVES; ANTAGONISTS AND INHIBITORS; CHEMISTRY; DRUG EFFECTS; ENZYME ACTIVE SITE; ENZYME SPECIFICITY; ESCHERICHIA COLI; GENE EXPRESSION; GENETICS; GROWTH, DEVELOPMENT AND AGING; KINETICS; METABOLISM; MICROBIAL SENSITIVITY TEST; MOLECULAR CLONING; SEQUENCE ALIGNMENT;

AMINO ACID ISOMERASES; AMINO ACID SEQUENCE; ANTITUBERCULAR AGENTS; BACTERIAL PROTEINS; BETA-ALANINE; CATALYTIC DOMAIN; CLONING, MOLECULAR; ENZYME INHIBITORS; ESCHERICHIA COLI; GENE EXPRESSION; KINETICS; MICROBIAL SENSITIVITY TESTS; MYCOBACTERIUM TUBERCULOSIS; PEPTIDOGLYCAN; PROTEIN BINDING; RECOMBINANT PROTEINS; SEQUENCE ALIGNMENT; SUBSTRATE SPECIFICITY;

EID: 84992650889     PISSN: 00664804     EISSN: 10986596     Source Type: Journal    
DOI: 10.1128/AAC.01249-16     Document Type: Article

References (47)

1. Zumla A, George A, Sharma V, Herbert N, Baroness Masham of Ilton. 2013. WHO's 2013 global report on tuberculosis: successes, threats, and opportunities. Lancet 382:1765-1767. http://dx.doi.org/10.1016/S0140-6736(13)62078-4.
2. Lambert MP, Neuhaus FC. 1972. Mechanism of D-cycloserine action: alanine racemase from Escherichia coli W. J Bacteriol 110:978-987.
3. Neuhaus FC, Lynch JL. 1964. The enzymatic synthesis of D-alanyl-D-alanine. 3. On the inhibition of D-alanyl-D-alanine synthetase by the antibiotic D-cycloserine. Biochemistry 3:471-480.
4. Prosser GA, de Carvalho LPS. 2013. Kinetic mechanism and inhibition of Mycobacterium tuberculosis D-alanine:D-alanine ligase by the antibiotic D-cycloserine. FEBS J 280:1150-1166. http://dx.doi.org/10.1111/febs.12108.
5. Prosser GA, de Carvalho LPS. 2013. Metabolomics reveal D-alanine: d-alanine ligase as the target of D-cycloserine in Mycobacterium tuberculosis. ACS Med Chem Lett 4:1233-1237. http://dx.doi.org/10.1021/ml400349n.
6. Prosser GA, de Carvalho LPS. 2013. Reinterpreting the mechanism of inhibition of Mycobacterium tuberculosis D-alanine:D-alanine ligase by D-cycloserine. Biochemistry 52:7145-7149. http://dx.doi.org/10.1021/bi400839f.
7. Badet B, Roise D, Walsh CT. 1984. Inactivation of the dadB Salmonella typhimurium alanine racemase by D and L isomers of beta-substituted alanines: kinetics, stoichiometry, active site peptide sequencing, and reaction mechanism. Biochemistry 23:5188-5194. http://dx.doi.org/10.1021/bi00317a016.
8. Esaki N, Walsh CT. 1986. Biosynthetic alanine racemase of Salmonella typhimurium: purification and characterization of the enzyme encoded by the alr gene. Biochemistry 25:3261-3267. http://dx.doi.org/10.1021/bi00359a027.
9. Roise D, Soda K, Yagi T, Walsh CT. 1984. Inactivation of the Pseudomonas striata broad specificity amino acid racemase by D and L isomers of beta-substituted alanines: kinetics, stoichiometry, active site peptide, and mechanistic studies. Biochemistry 23:5195-5201. http://dx.doi.org/10.1021/bi00317a017.
10. Manning JM, Merrifield NE, Jones WM, Gotschlich EC. 1974. Inhibition of bacterial growth by beta-chloro-D-alanine. Proc Natl Acad Sci USA71:417-421. http://dx.doi.org/10.1073/pnas.71.2.417.
11. David S. 2001. Synergic activity of D-cycloserine and beta-chloro-D-alanine against Mycobacterium tuberculosis. J Antimicrob Chemother 47:203-206. http://dx.doi.org/10.1093/jac/47.2.203.
12. Larrouy-Maumus G, Biswas T, Hunt DM, Kelly G, Tsodikov OV, de Carvalho LPS. 2013. Discovery of a glycerol 3-phosphate phosphatase reveals glycerophospholipid polar head recycling in Mycobacterium tuberculosis. Proc Natl Acad Sci USA110:11320-11325. http://dx.doi.org/10.1073/pnas.1221597110.
13. Raymond JB, Mahapatra S, Crick DC, Pavelka MS. 2005. Identification of the namH gene, encoding the hydroxylase responsible for the N-glycolylation of the mycobacterial peptidoglycan. J Biol Chem 280:326-333. http://dx.doi.org/10.1074/jbc.M411006200.
14. Wang E, Walsh C. 1978. Suicide substrates for the alanine racemase of Escherichia coli B. Biochemistry 17:1313-1321. http://dx.doi.org/10.1021/bi00600a028.
15. Zimmermann GR, Lehár J, Keith CT. 2007. Multi-target therapeutics: when the whole is greater than the sum of the parts. Drug Discov Today 12:34-42. http://dx.doi.org/10.1016/j.drudis.2006.11.008.
16. Mahapatra S, Scherman H, Brennan PJ, Crick DC. 2005. N Glycolylation of the nucleotide precursors of peptidoglycan biosynthesis of Mycobacterium spp. is altered by drug treatment. J Bacteriol 187:2341-2347. http://dx.doi.org/10.1128/JB.187.7.2341-2347.2005.
17. Poen S, Nakatani Y, Opel-Reading HK, Lassé M, Dobson RCJ, Krause KL. 2016. Exploring the structure of glutamate racemase from Mycobacterium tuberculosis as a template for anti-mycobacterial drug discovery. Biochem J 473:1267-1280. http://dx.doi.org/10.1042/BCJ20160186.
18. Potrykus J, Flemming J, Bearne SL. 2009. Kinetic characterization and quaternary structure of glutamate racemase from the periodontal anaerobe Fusobacterium nucleatum. Arch Biochem Biophys 491:16-24. http://dx.doi.org/10.1016/j.abb.2009.09.009.
19. Flynn JM, Downs DM. 2013. In the absence of RidA, endogenous 2-aminoacrylate inactivates alanine racemases by modifying the pyridoxal 5′-phosphate cofactor. J Bacteriol 195:3603-3609. http://dx.doi.org/10.1128/JB.00463-13.
20. Tanner ME. 2002. Understanding nature's strategies for enzyme-catalyzed racemization and epimerization. Acc Chem Res 35:237-246. http://dx.doi.org/10.1021/ar000056y.
21. Koo CW, Blanchard JS. 1999. Chemical mechanism of Haemophilus influenzae diaminopimelate epimerase. Biochemistry 38:4416-4422. http://dx.doi.org/10.1021/bi982911f.
22. Berkholz DS, Faber HR, Savvides SN, Karplus PA. 2008. Catalytic cycle of human glutathione reductase near 1 Å resolution. J Mol Biol 382:371-384. http://dx.doi.org/10.1016/j.jmb.2008.06.083.
23. Fisher SL. 2008. Glutamate racemase as a target for drug discovery. Microb Biotechnol 1:345-360. http://dx.doi.org/10.1111/j.1751-7915.2008.00031.x.
24. de Jonge BLM, Kutschke A, Uria-Nickelsen M, Kamp HD, Mills SD. 2009. Pyrazolopyrimidinediones are selective agents for Helicobacter pylori that suppress growth through inhibition of glutamate racemase (MurI). Antimicrob Agents Chemother 53:3331-3336. http://dx.doi.org/10.1128/AAC.00226-09.
25. de Jonge BLM, Kutschke A, Newman JV, Rooney MT, Yang W, Cederberg C. 2015. Pyridodiazepine amines are selective therapeutic agents for helicobacter pylori by suppressing growth through inhibition of glutamate racemase but are predicted to require continuous elevated levels in plasma to achieve clinical efficacy. Antimicrob Agents Chemother 59: 2337-2342. http://dx.doi.org/10.1128/AAC.04410-14.
26. de Dios A, Prieto L, Martín JA, Rubio A, Ezquerra J, Tebbe M, López de Uralde B, Martín J, Sánchez A, LeTourneau DL, McGee JE, Boylan C, Parr TR, Smith MC. 2002. 4-Substituted D-glutamic acid analogues: the first potent inhibitors of glutamate racemase (MurI) enzyme with antibacterial activity. J Med Chem 45:4559-4570. http://dx.doi.org/10.1021/jm020901d.
27. Soper TS, Jones WM, Lerner B, Trop M, Manning JM. 1977. Inactivation of bacterial D-amino acid transaminase by beta-chloro-D-alanine. J Biol Chem 252:3170-3175.
28. LeMagueres P, Im H, Ebalunode J, Strych U, Benedik MJ, Briggs JM, Kohn H, Krause KL. 2005. The 1.9 A crystal structure of alanine racemase from Mycobacterium tuberculosis contains a conserved entryway into the active site. Biochemistry 44:1471-1481. http://dx.doi.org/10.1021/bi0486583.
29. Ernst DC, Lambrecht JA, Schomer RA, Downs DM. 2014. Endogenous synthesis of 2-aminoacrylate contributes to cysteine sensitivity in Salmonella enterica. J Bacteriol 196:3335-3342. http://dx.doi.org/10.1128/JB.01960-14.
30. Lambrecht JA, Schmitz GE, Downs DM. 2013. RidA proteins prevent metabolic damage inflicted by PLP-dependent dehydratases in all domains of life. mBio 4:e00033-13. http://dx.doi.org/10.1128/mBio.00033-13.
31. Whalen WA, Wang MD, Berg CM. 1985. beta-Chloro-L-alanine inhibition of the Escherichia coli alanine-valine transaminase. J Bacteriol 164:1350-1352.
32. Cava F, de Pedro MA, Lam H, Davis BM, Waldor MK. 2011. Distinct pathways for modification of the bacterial cell wall by non-canonical D-amino acids. EMBO J 30:3442-3453. http://dx.doi.org/10.1038/emboj.2011.246.
33. Chen JM, Uplekar S, Gordon SV, Cole ST. 2012. A point mutation in cycA partially contributes to the D-cycloserine resistance trait of Mycobacterium bovis BCG vaccine strains. PLoS One 7:e43467. http://dx.doi.org/10.1371/journal.pone.0043467.
34. Lambrecht JA, Flynn JM, Downs DM. 2012. Conserved YjgF protein family deaminates reactive enamine/imine intermediates of pyridoxal 5′-phosphate (PLP)-dependent enzyme reactions. J Biol Chem 287:3454-3461. http://dx.doi.org/10.1074/jbc.M111.304477.
35. Thakur KG, Praveena T, Gopal B. 2010. Mycobacterium tuberculosis Rv2704 is a member of the YjgF/YER057c/UK114 family. Proteins 78:773-778.
36. Niehaus TD, Gerdes S, Hodge-Hanson K, Zhukov A, Cooper AJL, ElBadawi-Sidhu M, Fiehn O, Downs DM, Hanson AD. 2015. Genomic and experimental evidence for multiple metabolic functions in the RidA/YjgF/YER057c/UK114 (Rid) protein family. BMC Genomics 16:382. http://dx.doi.org/10.1186/s12864-015-1584-3.
37. Sengupta S, Shah M, Nagaraja V. 2006. Glutamate racemase from Mycobacterium tuberculosis inhibits DNA gyrase by affecting its DNA-binding. Nucleic Acids Res 34:5567-5576. http://dx.doi.org/10.1093/nar/gkl704.
38. Sengupta S, Nagaraja V. 2008. Inhibition of DNA gyrase activity by Mycobacterium smegmatis MurI. FEMS Microbiol Lett 279:40-47. http://dx.doi.org/10.1111/j.1574-6968.2007.01005.x.
39. May M, Mehboob S, Mulhearn DC, Wang Z, Yu H, Thatcher GRJ, Santarsiero BD, Johnson ME, Mesecar AD. 2007. Structural and functional analysis of two glutamate racemase isozymes from Bacillus anthracis and implications for inhibitor design. J Mol Biol 371:1219-1237. http://dx.doi.org/10.1016/j.jmb.2007.05.093.
40. Chacon O, Bermudez LE, Zinniel DK, Chahal HK, Fenton RJ, Feng Z, Hanford K, Adams LG, Barletta RG. 2009. Impairment of D-alanine biosynthesis in Mycobacterium smegmatis determines decreased intracellular survival in human macrophages. Microbiology 155:1440-1450. http://dx.doi.org/10.1099/mic.0.024901-0.
41. Feng Z, Barletta RG. 2003. Roles of Mycobacterium smegmatis D-alanine: D-alanine ligase and D-alanine racemase in the mechanisms of action of and resistance to the peptidoglycan inhibitor D-cycloserine. Antimicrob Agents Chemother 47:283-291. http://dx.doi.org/10.1128/AAC.47.1.283-291.2003.
42. Mengin-Lecreulx D, Flouret B, van Heijenoort J. 1982. Cytoplasmic steps of peptidoglycan synthesis in Escherichia coli. J Bacteriol 151:1109-1117.
43. Doublet P, van Heijenoort J, Bohin JP, Mengin-Lecreulx D. 1993. The murI gene of Escherichia coli is an essential gene that encodes a glutamate racemase activity. J Bacteriol 175:2970-2979.
44. Lundqvist T, Fisher SL, Kern G, Folmer RHA, Xue Y, Newton DT, Keating TA, Alm RA, de Jonge BLM. 2007. Exploitation of structural and regulatory diversity in glutamate racemases. Nature 447:817-822. http://dx.doi.org/10.1038/nature05689.
45. Cáceres NE, Harris NB, Wellehan JF, Feng Z, Kapur V, Barletta RG. 1997. Overexpression of the D-alanine racemase gene confers resistance to D-cycloserine in Mycobacterium smegmatis. J Bacteriol 179:5046-5055.
46. Reitz RH, Slade HD, Neuhaus FC. 1967. The biochemical mechanisms of resistance by streptococci to the antibiotics D-cycloserine and O-carbamyl-D-serine. Biochemistry 6:2561-2570. http://dx.doi.org/10.1021/bi00860a038.
47. Ashiuchi M, Yoshimura T, Esaki N, Ueno H, Soda K. 1993. Inactivation of glutamate racemase of Pediococcus pentosaceus with L-serine O-sulfate. Biosci Biotechnol Biochem 57:1978-1979. http://dx.doi.org/10.1271/bbb.57.1978.