Bacterial Glutathione - American Chemical Society

Chapter 13

Bacterial Glutathione S-Transferases and the Detoxification of Xenobiotics: Dehalogenation through Glutathione Conjugation and Beyond Downloaded by STANFORD UNIV GREEN LIBR on September 17, 2012 | http://pubs.acs.org Publication Date: December 1, 2000 | doi: 10.1021/bk-2001-0777.ch013

Stéphane Vuilleumier Institut für Mikrobiologie, ETH Zürich, CH-8092 Zürich, Switzerland

Several dozen sequences of bacterial glutathione S-transferases (GSTs) are now known, mainly as the result of whole genome sequencing efforts. So far, only a minority of bacterial GSTs have been characterized at the biochemical level. Some GSTs were shown to catalyze dehalogenation reactions, and several others also appear to be associated with metabolic pathways for the degradation of halogenated xenobiotic compounds. The modest sequence similarity observed between bacterial members of this protein family further suggests that they may catalyze a wide range of glutathione-dependent reactions within the conserved canonical GST structural framework. Characterization of the physiological function of bacterial GSTs and of the bacterial metabolism associated with glutathione conjugation reactions will be the key for the implementation of strategies for the detoxification of xenobiotics based on GSTs in bacteria.

Glutathione S-transferases (GSTs) are ubiquitous and versatile catalysts that detoxify xenobiotics and reactive endogenous compounds by conjugation to glutathione. GSTs from mammals have been extensively studied because of their association with cancer (1). In plants, the detoxification of pesticides, herbicides and environmental pollutants often involves GST enzymes (2). The resulting conjugates are then, either transported to the vacuole for storage and subsequent export (3), or processed further (4). Complete degradation (mineralization) of these conjugates appears to be rare. The occurrence of GST-dependent pathways in bacteria for the detoxification and degradation of xenobiotics, and of herbicides in particular, is documented in several

240

© 2001 American Chemical Society

In Pesticide Biotransformation in Plants and Microorganisms; Hall, J., et al.; ACS Symposium Series; American Chemical Society: Washington, DC, 2000.

Downloaded by STANFORD UNIV GREEN LIBR on September 17, 2012 | http://pubs.acs.org Publication Date: December 1, 2000 | doi: 10.1021/bk-2001-0777.ch013

241 reports. Several soil bacteria were found to contain GST activity and to catalyze the formation of glutathione conjugates of the herbicide alachlor (5,6), but the enzymes responsible for these transformations remain to be characterized. The importance of GSTs in the degradation of xenobiotics in the environment is further indicated by the detection of metabolites of herbicides in soil and groundwater that contain sulfur, such as the corresponding thiols, thioethers, sulfoxides, sulfones and sulfonic acids (7,8). However, the portion of this metabolism due to bacterial action remains to be determined. Even more remains to be learned about the regulation of GST expression, the uptake of pesticides and other hydrophobic GST substrates, and on the excretion, processing and toxicity of glutathione conjugates in bacteria. This is somewhat of a paradox considering the steadily increasing number of bacterial genes annotated as GSTs in sequence databases (Table I). This lack of knowledge about the physiological roles of bacterial GSTs also contrasts with the widespread interest in biodegradation and biodetoxification strategies relying on bacterial systems. Compared to plants, bacterial systems offer major technical advantages, including rapid growth, ease of molecular genetic methods, transformation by plasmids, and availability of comprehensive sequence data generated in genome sequencing projects. With regard to biodegradation approaches for remediation, bacteria often have the additional asset of permitting mineralization of the compounds of interest. This paper summarizes results and information on bacterial GSTs obtained since this subject was last reviewed (9). Aspects of the sequence and structure of bacterial GSTs and of the reactions catalyzed by their best characterized representatives will be addressed, as well as the physiological role of these enzymes, the cellular processes associated with G S T catalysis, and the potential of bacteria expressing GSTs for remediation applications.

Sequence and structure similarity in bacterial GST enzymes Enzymes with glutathione transferase activity are found in all realms of aerobic life. They appear to have evolved through both convergent and divergent pathways, as evidenced by differences in gene sequence, enzyme structure, and in amino acid residues involved in catalysis (70). Compared to representatives of the mammalian alpha, mu and pi classes of GSTs, bacterial and plant GSTs show extensive sequence variation and build only loosely defined groups (77). Nevertheless, similarity searches of newly sequenced putative bacterial GST genes almost exclusively retrieve hits to other G S T sequences. Consequently, these new sequences are usually annotated as GSTs, despite the fact that the reactions catalyzed by the corresponding proteins are unknown. In addition, it seems unlikely that the glutathione-dependent stress proteins similar in sequence to the A/-terminal domain of GSTs (12) actually catalyze detoxification reactions strictu sensu. The GST-like domain of one such protein, Ure2 from yeast, which displays prion-like behaviour, was recently proposed to stabilize the shorter prion-determining domain of Ure2 against prion formation (13). Clearly, more stringent criteria would be needed to discriminate between such protein sequences and those of GSTs involved in the detoxification of toxic



b

Cycloclasticus oligotrophus polycyclic aromatics?

Sphingomonas sp. RW1

Pseudomonas sp. U2

Q46153

007878

086043

086923

AF10913 Sinorhizobium meliloti 1

XylK

OrfE3

NagL

Orf3

MaiA

Q52828

P15214

GstA

GstB

Proteus mirabilis

Rhizobium leguminosarum

AJ249207 Rhodococcus sp. AD45

plasmid pUOH109

c

antibiotic inactivation?

plant-bacterial interactions?

epoxide ring-opening

2-haloacid dehalogenation?

maleylacetoacetate isomerase?

chlorinated gentisates?

chlorinated gentisates?

chlorinated dibenzofurans and dioxins?

chlorinated biphenyls?

3

c

9

l0

b

GT(10" /54%) [5]

65

YfcG (10* /26%)[6]

13

6

YfcG (10- /36%)[4]

GT(10^/17%) [2]

YliJ (10- /24%)[4]

12

SspA(10' /23%) [1]

6

SspA(10- /19%)[2]

GT(10- /42%) [5]

44

51

GT(10" /48%) [5]

52

YfcG(10- /21%)[4]

GT (10- /21%) [2]

-

-

YliJ(10- /21%)[2]

6

Escherichia coli

16

GstE(10- /26%)[7]

13

GstM (10""/42%) [10]

26

GstK (10- /31%) [2]

40

GstF(10- /37%) [6]

GstP(10- /41%) [8]

39

GstB(10- /33%) [9]

GstQaO^/SO^o) [6]

50

GstQ(10' /47%)[4]

12

GstQ(10- /26%) [10]

13

GstB(10- /27%) [8]

48

GstF(10" /47%)[7]

I0

GstN(10- /29%)[2]

5

GstE(10' /29%) [3]

8

GstN(10- /24%)[4]

9

GstA(10- /21%)[4]

P. aeruginosa

Best hit (E value / % id.) [number of hits]

The E. coli genome contains 8 GST-like genes (14). The 17 GST-like genes detected in the preliminary version of the complete genome of Pseudomonas aeruginosa (15) were arbitrarily labelled GstA through GstQ in the order they appear in the 6.2 MB genome sequence. Accession numbers arefromthe Swissprot/Trembl protein database except those in italics. Significant hits with an E-value of < 10" in a GAPPED-BLAST search (16) and which extend over 100 amino acids are shown. Identity in percent is calculated for the shorter of the two sequences compared.

a

Burkholderia sp. LB400

Q59721

BphK

Isol

Burkholderia cepacia AC 1100 2,4,5-trichlorophenoxyacetic acid?

Q45073

Orf3

D17523

Sphingomonas paucimobilis P-etherase

P30347

LigF

Sphingomonas sp. RW5

Sphingomonas chlorophenolica tetrachlorohydroquinone reductase

Q03520

PcpC

dichloromethane dehalogenase

Methylophilus sp. DM11

P43387

dichloromethane dehalogenase

Function or degradative gene cluster

DcmA

Methylobacterium sp. DM4

Organism

P21161

Acc. No.

DcmA

Name

8

Table I. Sequence Similarity of Bacterial GSTs to Genomic Sets of GST Genes


6

243


chemicals. Nevertheless, the flood of new GST-like sequences resulting from genome D N A sequencing projects in prokaryotes carries two important messages. First, these studies indicate that a single bacterium may contain a large set of GST genes whose size and content may vary significantly (Table I). Second, many new bacterial GSTlike genes, listed in Table I, appear to be associated with operons and gene clusters involved in the degradation (and often the dehalogenation) of xenobiotics. The 4.6 megabase genome of Escherichia coli (17) contains 8 GST-like genes (14), compared to 17 for the Pseudomonas aeruginosa genome comprised of 6.2 megabases (75). Interestingly, only 4 of the detected GST genes appear to have close homology (>40% sequence identity at the protein level) in both genomes. In addition, GST sequences found in biodegradation-associated gene clusters from bacteria are often similar to only a subset of the GST sequences encoded in a given genome (Table I). Thus, overall sequence variability within the bacterial GST family of proteins may well be much larger than that found in a single genome. Nevertheless, the Pseudomonas set appears to be more closely related overall to bacterial biodegradation-associated GSTs than the E. coli one (Table I). In no case has the physiological role of a GST detected by whole-genome sequencing yet been determined. This may continue to hold true in the near future for several reasons. First, the observed low level of sequence identity in bacterial GSTs makes it unrealistic to decide on the function of a given GST from sequence alone. Second, bacterial GSTs of known function catalyze varied reactions (Table I) and often lack activity with standard model GST substrates such as l-chloro-2,4dinitrobenzene (CDNB). Third, a phenotype may be difficult to determine in specific GST knockout mutants, since the large sets of GST-like genes found in genomes may lead to partial complementation of the function of the disrupted gene. In addition, a classical growth phenotype in a GST-minus mutant is not expected a priori, because mutants of E. coli lacking glutathione are still viable. Insights into the role of the proteins encoded by putative GST genes detected in genome sequencing projects will most likely arise from gene expression studies under a wide variety of conditions. It is important to note that the extensive sequence variation in the GST family does not appear to significantly affect the structural framework within which GSTs catalyze glutathione conjugation reactions (Figure 1). For example, a GST from A. thaliana involved in herbicide tolerance (19), two bacterial enzymes of known structure from E. coli (22) and Proteus mirabilis (18), and the human GST theta 2-2 enzyme (20) used as a model for the dichloromethane-active human GST theta 1-1 enzyme (hGSTTl-1) (21), can be structurally aligned over 117 residues. The structural similarity between these proteins appears even closer in pairwise comparisons, despite sequence identity below 20% and only 15 identical residues in the four proteins (Table II). Thus, the GST structural framework has served as an evolutionarily stable scaffold for the development of detoxification catalysts relying



Figure 1. Comparison of the aligned structures of the bacterial GST from P. mirabilis ((18); enzyme-GSH mixed disulfide), the alachlor-active GST from Arabidopsis thaliana ((19); FOE-4059 glutathione conjugate) and a model of the human GSTT1 (20) based on the human GSTT2 structure (21).


t

245 on glutathione conjugation. This fact is already being exploited in the laboratory, with the application of methods of phage display (23,24) and D N A shuffling (25) for the selection of GST catalysts with the desired specificity in bacteria.

Table II. Percent Structural vs. Sequence Similarity Between Glutathione S-Transferases of K n o w n X - R a y Structure E.c.

P. m.

A. th.

hGSTTl

Escherichia coli f l A O F )

a

54

18

20

Proteus mirabilis (1PMT)

98

20

16


Organism (PDB entry)

Arabidopsis thaliana (1BX9)

77

70

b

70

71

human GSTT1 model (3LJR ) a

b

18 74

Left of diagonal: aligned residues (%); right of diagonal: identical residues (%). hGSTTl model based on the the 55% identical hGSTT2 X-ray structure (21).

Bacterial GSTs of K n o w n Function Bacterial dichloromethane dehalogenases are the oldest known examples of bacterial GSTs (26). They are perhaps also the most atypical, both by sequence and by the reactions they catalyze (Figure 2A). Protein engineering studies of the enzyme from Methylophilus sp. DM11 (27-29) have enabled (to some degree) the elucidation of its catalytic determinants. Its reaction mechanism is still poorly understood, but thought to involve a reactive, short-lived intermediate, S-chloromethylglutathione. Recent work has addressed the toxicity associated with GST-dependent turnover of dichloromethane ( D C M ) observed for the closest homologs of bacterial D C M dehalogenases, the GSTT1-1 enzymes from mammals (30). This toxicity was surprising since no detrimental effects were observed in methylotrophic bacteria growing with D C M as the unique carbon source by virtue of their D C M dehalogenase. It was recently shown that the rat GSTT1-1 enzyme has much lower affinity for D C M than bacterial D C M dehalogenases, despite affording a higher turnover rate at very high substrate concentrations (31). Furthermore, expression of rat GSTT1-1 in the presence of D C M (unlike that of bacterial D C M dehalogenase) was toxic in the Methylobacterium sp. D M 4 background, and mutagenic in a Salmonella Ames tester strain (31). Clearly, only bacterial versions of DCM-active GSTs allow the safe degradation of this toxic compound. The comparison of D C M converting G S T enzymes from mammals and bacteria thus provides a vivid example that proteins with similar sequences that catalyze the same transformation, may nonetheless have strikingly different consequences for the host organism.



246

Figure 2. Some reactions catalysed by different bacterial GSTs. A) dichloromethane dehalogenation, B) reductive dehalogenation of chlorinated hydroquinones, C) epoxide ring-opening, D) carbon-carbon double bond isomerization.



247 Another atypical G S T from bacteria is the reductive dehalogenase tetrachlorohydroquinone reductase (PcpC) from Sphingomonas chlorophenolica, which catalyzes the stepwise glutathione-dependent dehalogenation of tetrachlorohydroquinone to dichlorohydroquinone with concomitant oxidation of glutathione (Figure 2B). The PcpC sequence is one of the most divergent within known bacterial GSTs (32), together with that of the p-etherase LigF from Sphingomonas paucimobilis involved in lignin degradation (33) (Table I). The sequence of the functionally related 2,5-dichlorohydroquinone reductive dehalogenase (LinD) involved in y-hexachlorocyclohexane degradation (34) is even more distantly related. These three GST-like proteins all oxidize glutathione during catalysis, thus demonstrating the existence of other functions of bacterial GSTs beyond conjugation. The PcpC enzyme was recently characterized in more detail (32,35,36). A n unexpected finding was the transient formation of a mixed disulfide of glutathione with residue cysteine 13 of the protein during turnover (35). The thiol form of the enzyme is then regenerated by glutathione-dependent reduction, yielding glutathione disulfide. Interestingly, the structures of glutaredoxins, proteins which catalyze reversible oxidation/reduction of protein disulfide groups and glutathionecontaining mixed disulfides (37), share a common structural fold with GSTs despite negligible sequence identity (38). A mixed disulfide between enzyme and glutathione was observed in the X-ray structure of the Proteus mirabilis glutathione S-transferase ((18), Figure 1), and the GST from Rhizobium leguminosarum may also form a mixed disulfide with glutathione (39). It is not yet known, however, whether a mixed disulfide with glutathione is relevant for the reaction catalyzed by GSTs other than PcpC. A n exciting recent development in the field of bacterial GSTs was the characterization of the biodegradative pathway for the degradation of isoprene and chlorinated ethenes, in which a GST enzyme features prominently (40-42). The key step in this pathway involves the GST-catalyzed opening of an epoxide ring (Figure 2C). Somewhat surprisingly, the bacterium effecting these transformations is a grampositive Rhodococcus strain. With a few exceptions, gram-positive bacteria appear to be devoid of glutathione (43). The enzyme responsible for the epoxide ring opening reaction was purified and characterized, and the corresponding isol gene cloned and sequenced ((41), see Table I). Sequence similarity of the Isol G S T to other proteins was modest and limited to only a few other G S T sequences. Another glutathionedependent epoxide ring opening enzyme, FosA, affords fosfomycin resistance in the host bacteria (44,45). In contrast to the Rhodococcus enzyme, however, this enzyme belongs to a completely different structural class of protein catalysts, i . e., metalloenzymes that include glyoxalase and extradiol dioxygenases, with no detectable sequence similarity to bona fide GSTs. The Rhodococcus enzyme displays a K for glutathione well above 10 m M , in contrast to a high affinity for isoprene monoxide and 1,2-cw-dichloroepoxyethane (both K = 0.1 mM). The latter substrate is postulated to decay spontaneously to oxaldehyde by HC1 elimination from the glutathione adduct, followed by hydrolysis and subsequent elimination of a second molecule of HC1 (40). Thus, this enzyme is both a bona fide glutathione conjugating m

m



248 GST and a dehalogenase. The route for the further degradation of the stable glutathione conjugate of isoprene epoxide in Rhodococcus is still unknown, although some of the genes found at the same locus as the GST gene may be involved in this process (41). Further investigations with this system should therefore yield novel insights on the catabolism of glutathione conjugates in bacteria. The dependence of enzyme-catalyzed carbon-carbon double bond isomerization reactions on glutathione was already investigated in detail in the sixties and seventies (46-48). A n unexpected connection of glutathione-dependent isomerases with GSTcatalyzed dehalogenation reactions recently became apparent. The human G S T gene defining a new class of GSTs, zeta, was demonstrated to encode an enzyme catalyzing the dehalogenation of 2-haloacids (49,50). Surprisingly, the same gene was also shown to complement a gene defect in the metabolism of tyrosine at the level of homogentisate oxidation (51). The corresponding enzyme had the function of a maleylacetoacetate isomerase ((52), Figure 2D). Genes encoding proteins similar to this bifunctional human G S T were found in bacterial operons involved in the degradation of aromatic compounds such as homogentisate and gentisate (53-56), Table I). Since the corresponding bacteria were investigated for their ability to degrade halogenated aromatics, this suggests the possibility that the corresponding proteins, as the human enzyme, may act both as dehalogenases and as isomerases. The verification of this hypothesis, unfortunately, requires relatively unstable substrates that are not commercially available. However, the repeated findings of GST-like genes in gene clusters involved in the ring opening of aromatic compounds by dioxygenases certainly indicate that the corresponding gene products play a role in the catabolism of aromatic compounds.

GST-associated metabolism in bacteria With respect to GST-dependent bacterial transformation of xenobiotics, many important questions remain to be investigated. Can glutathione conjugates be excreted, or indeed taken up by bacteria, or are they mainly metabolized intracellularly? What are the enzymes and proteins required in these processes? What is the toxicity of xenobiotics and of their corresponding glutathione conjugates and degradation products to bacteria? Do such compounds elicit the induction of other genes? These questions can be addressed experimentally, as several recent studies have begun to demonstrate. The penetration of xenobiotics into bacterial cells and the formation and localization of glutathione conjugates can be traced using labelled substrates (6,57). The occurrence and role of glutathione conjugate transporters can be investigated using uncouplers and inhibitors (58). In contrast to the situation in plants, however, only a few studies of the catabolism of glutathione conjugates in bacteria have yet been reported. The glutathione conjugate of alachlor was proposed to be processed by a specific protease, y-glutamyltranspeptidase, and by cysteine plyase, since these activities were detected in cell-free extracts of alachlor-conjugating bacteria (6).



249 Another overlooked aspect of the metabolism associated with GST-dependent degradation of xenobiotics regards the toxicity of GST substrates and of their corresponding glutathione conjugates and metabolites. Glutathione conjugation is generally assumed to cause the detoxification of electrophilic toxic chemicals, but some glutathione conjugates, such as that of C D N B , are actually more toxic than the parent compounds (59). In the case of GST-mediated D C M catabolism, the postulated short-lived S-chloromethylglutathione conjugate is a known D N A alkylating agent thought to be responsible for the mutagenicity associated with D C M (60). Mutants of Methylobacterium sp. D M 4 , recently obtained by minitransposon mutagenesis, lost the ability to grow on D C M as the sole carbon source, but still possessed an active D C M dehalogenase/GST. The genes carrying an insertional lesion in these mutants were involved in D N A repair (unpublished results). Glutathione-conjugated products of GST-catalyzed reactions may also have a signalling function in cellular metabolism. For example, the K e f proteins of E. coli, induced by certain glutathione conjugates, cause potassium efflux with associated proton influx, leading to protection against the toxicity of electrophilic compounds (61). Finally, the uptake of GST substrates by bacteria is another topic that deserves closer attention in the future. Preferential uptake of a GST substrate by some bacteria may also strongly determine GST-based metabolism, as observed by the growth behavior of different DCM-degrading methylotrophic bacteria. When D C M was present in limiting amounts as the sole carbon source, the measured growth rate was significantly higher than that expected from the amount and specific activity of the D C M dehalogenase/GST in the case of Methylobacterium sp. D M 4 , but not with Methylophilus sp. DM11 (62). This tentatively suggests that a specific uptake system for D C M was induced in the Methylobacterium strain under these conditions. Interestingly, a high-affinity substrate uptake system was recently described in detail for a methylotrophic bacterium degrading short-chain alkylamides and urea (63).

Applications of bacteria expressing biodegradative G S T enzymes Considering the wide scope of reactions catalyzed by bacterial GSTs of known function, such proteins and the bacteria that express them appear as attractive candidates for biodegradation and biodetoxification applications. Bacteria with efficient glutathione-based degradation pathways also have potential in combination with phytoremediation approaches, which involve the use of plants to degrade persistent xenobiotics (64). Enhanced detoxification of xenobiotics by bacteria in soil in the presence of plants has been repeatedly observed in field studies. In addition, bacteria may be well-suited to further degrade potentially toxic glutathione conjugates of xenobiotics produced by plants. For remediation applications based on GST-expressing bacteria to be developed, however, an increased knowledge of the function and substrate specificity of bacterial GSTs is required. The screening of soil bacterial isolates to detect glutathione-dependent transformation of target xenobiotics (6) should constitute a choice approach towards this goal. Concomitantly and


250


importantly, the pathways of xenobiotic degradation involving GSTs, the metabolic processes associated with the toxicity of the electrophilic substrates and of the corresponding glutathione conjugates, as well as the distribution of bacteria with prominent GST-dependent catabolic pathways in different environments also need to be characterized. Clearly, future work in this area in the next few years will set the stage for the implementation of GST-based strategies for the detoxification of xenobiotics using bacterial systems.

Acknowledgements Funding by grant 31-50602.97 of the Swiss National Research Foundation is gratefully acknowledged.

Literature Cited 1. 2. 3. 4.

5.

6. 7. 8. 9. 10. 11. 12. 13. 14. 15. 16. 17.

McLellan, L . I.; Wolf, C. R. Drug Res. Updates 1999, 2, 153-164. Marrs, K. A . Annu. Rev. Plant Physiol. Plant Mol. Biol. 1996, 47, 127-158. Rea, P. A . ; L i , Z.-D.; L u , Y.-P.; Drozdowicz, Y. M.; Martinoia, E. Annu. Rev. Plant Physiol. Plant Mol. Biol. 1998, 49, 727-760. Lamoureux, G . L . ; Rusness, D . G . In Sulfur Nutrition and Assimilation in Higher Plants; De Kok, L. J.; Stulen, I.; Rennenberg, H . ; Brunold, C.; Rauser, W . E., Eds.; SPB Academic Publishing: The Hague, 1993; pp 221-237. Zablotowicz, R. M.; Hoagland, R. E.; Locke, M. A . In Bioremediation Through Rhizosphere Technology; Anderson, T. A . ; Coats, J. R., Eds.; American Chemical Society: Washington, D C , 1994; V o l . 563, pp 184-198. Zablotowicz, R. M.; Hoagland, R. E.; Locke, M. A . ; Hickey, W . J. Appl. Environ. Microbiol. 1995, 61, 1054-1060. Feng, P. C. C. Pest. Biochem. Physiol. 1991, 40, 136-142. Field, J. A.; Thurman, E . M. Environ. Sci. Technol. 1996, 30, 1413-1418. Vuilleumier, S. J. Bacteriol. 1997, 179, 1431-1441. Armstrong, R. N. Chem. Res. Toxicol 1997, 10, 2-18. Snyder, M. J.; Maddison, D . R. DNA Cell Biol. 1998, 16, 1373-1384. Koonin, E . V.; Mushegian, A. R.; Tatusov, R. L.; Altschul, S. F.; Bryant, S. H . ; Bork, P.; Valencia, A . Protein Sci. 1994, 3, 2045-2054. Perrett, S.; Freeman, S. J.; Butler, P. J. G.; Fersht, A. R. J. Mol. Biol. 1999, 290, 331-345. Vuilleumier, S.; Gisi, D . ; Stumpp, M. T.; Leisinger, T. Clin. Chem. Enzymol. Commun. 1999, 8, 367-378. Pseudomonas Genome Project, U R L http://pseudomonas.genome.com. Altschul, S. F.; Madden, T. L . ; Schaeffer, A . A . ; Zhang, J.; Zhang, Z.; Miller, W.; Lipman, D . J. Nucleic Acids Res. 1997, 25, 3389-3402. Blattner, F. R.; Plunkett, G., III; Bloch, C. A.; Perna, N. T.; Burland, V.; Riley, M.; Collado Vides, J.; Glasner, J. D.; Rode, C. K.; Mayhew, G . F.; Gregor, J.;


251

18. 19. 20.


21. 22. 23.

24. 25. 26. 27. 28. 29. 30. 31. 32. 33. 34. 35. 36. 37. 38. 39. 40.

Davis, N. W.; Kirkpatrick, H . A.; Goeden, M. A . ; Rose, D . J.; Mau, B.; Shao, Y. Science 1997, 277, 1453-1462. Rossjohn, J.; Polekhina, G.; Feil, S. C.; Allocati, N.; Masulli, M.; D i Ilio, C.; Parker, M. W . Structure 1998, 6, 721-734. Prade, L . ; Huber, R.; Bieseler, B . Structure 1998, 6, 1445-1452. Rossjohn, J.; McKinstry, W . J.; Oakley, A . J.; Verger, D . ; Flanagan, J.; Chelvanayagam, G.; Tan, K.-L.; Board, P. G.; Parker, M. W . Structure 1998, 6, 309-322. Flanagan, J. U.; Rossjohn, J.; Parker, M. W.; Board, P. G.; Chelvanayagam, G. Proteins Struct. Fund. Genet. 1998, 33, 444-454. Nishida, M.; Harada, S.; Noguchi, S.; Satow, Y.; Inoue, H . ; Takahashi, K . J. Mol. Biol. 1998, 281, 135-147. Mannervik, B . ; Cameron, A. D . ; Fernandez, E.; Gustafsson, A . ; Hansson, L . O.; Jemth, P.; Jiang, F. Y.; Jones, T. A . ; Larsson, A. K . ; Nilsson, L . O.; Olin, B . ; Pettersson, P. L.; Ridderstrom, M.; Stenberg, G.; Widersten, M. Chem. Biol. Int. 1998, 112, 15-21. Demartis, S.; Huber, A.; Viti, F.; Lozzi, L.; Giovannoni, L . ; Neri, P.; Winter, G.; Neri, D . J. Mol. Biol. 1999, 286, 617-633. Hansson, L . O.; Bolton Grob, R.; Massoud, T.; Mannervik, B . J. Mol. Biol. 1999, 287, 265-276. Leisinger, T.; Bader, R.; Hermann, R.; Schmid-Appert, M.; Vuilleumier, S. Biodegradation 1994, 5, 237-248. Vuilleumier, S.; Leisinger, T. Eur. J. Biochem. 1996, 239, 410-417. Vuilleumier, S.; Sorribas, H . ; Leisinger, T. Biochem. Biophys. Res. Commun. 1997, 238, 452-456. Cai, B.; Vuilleumier, S.; Wackett, L . P. Ann. NY Acad. Sci. 1998, 864, 210-213. Thier, R.; Taylor, J. B . ; Pemble, S. E.; Humphreys, W. G.; Persmark, M.; Ketterer, B.; Guengerich, F. P. Proc. Natl. Acad. Sci. USA 1993, 90, 8576-8580. Gisi, D.; Leisinger, T.; Vuilleumier, S. Arch. Toxicol. 1999, 73, 71-79. McCarthy, D . L . ; Navarrete, S.; Willett, W . S.; Babbitt, P. C.; Copley, S. D. Biochemistry 1996, 35, 14634-14642. Masai, E.; Katayama, Y.; Kubota, S.; Kawai, S.; Yamasaki, M.; Morohoshi, N. FEBS Lett. 1993, 323, 135-140. Miyauchi, K . ; Suh, S. K . ; Nagata, Y . ; Takagi, M. J. Bacteriol. 1998, 180, 13541359. McCarthy, D . L . ; Louie, D . F.; Copley, S. D . J. Amer. Chem. Soc. 1997, 119, 11337-11338. Copley, S. D . Curr. Op. Chem. Biol. 1998, 2, 613-617. Nordstrand, K . ; Åslund, F.; Holmgren, A.; Otting, G.; Berndt, K . D . J. Mol. Biol. 1999, 286, 541-552. Martin, J. L. Structure 1995, 3, 245-250. Alkafaf, N. K. T.; Yeoman, K . H . ; Wexler, M.; Hussain, H . ; Johnston, A . W . B . Microbiology 1997, 143, 813-822. van Hylckama Vlieg, J. E . T.; Kingma, J.; van den Wijngaard, A. J.; Janssen, D . B . Appl. Environ. Microbiol. 1998, 64, 2800-2805.



252 41. van Hylckama Vlieg, J. E . T. Ph. D. Thesis, Rijksuniversiteit, Groningen, 1999. 42. van Hylckama Vlieg, J. E. T.; Kingma, J.; Kruizinga, W.; Janssen, D . B . J. Bacteriol. 1999, 181, 2094-2101. 43. Sherrill, C.; Fahey, R. C. J. Bacteriol. 1998, 180, 1454-1459. 44. Armstrong, R. N. Curr. Op. Chem. Biol. 1998, 2, 618-623. 45. Armstrong, R. N.; Bernat, B . A . In Enzymatic Mechanisms; Frey, P. A . ; Northrop, B., Eds.; IOS Press: Amsterdam, 1999; pp 215-223. 46. Lack, L . J. Biol. Chem. 1961, 236, 2835-2840. 47. Crawford, R. L.; Frick, T. D. Appl. Environ. Microbiol. 1977, 34, 170-174. 48. Seltzer, S. In Glutathione, Chemical, Biochemical and Medical Aspects; Dolphin, D.; Avramovic, O.; Poulson, R., Eds.; Wiley-Interscience: New York, 1989; V o l . B , pp 733-751. 49. Tong, Z.; Board, P. G.; Anders, M. W. Biochem. J. 1998, 371, 371-374. 50. Tong, Z.; Board, P. G.; Anders, M. W. Chem. Res. Toxicol. 1998, 11, 1332-1338. 51. Fernández-Cañón, J. M.; Peñalva, M. A. J. Biol. Chem. 1998, 273, 329-337. 52. Fernández-Cañón, J. M.; Hejna, J.; Reifsteck, C.; Olson, S.; Grompe, M. Genomics 1999, 58, 263-269. 53. Armengaud, J.; Timmis, K . N. Eur. J. Biochem. 1997, 247, 833-842. 54. Fuenmayor, S. L . ; Wild, M.; Boyes, A. L.; Williams, P. A. J. Bacteriol. 1998, 180, 2522-2530. 55. Werwath, J.; Arfmann, H.-A.; Pieper, D . H . ; Timmis, K . H.; Wittich, R . - M . J. Bacteriol. 1998, 180, 4171-4176. 56. Milcamps, A . ; deBruijn, F. J. Microbiology 1999, 145, 935-947. 57. Coleman, J. O. D . ; Randall, R.; Blake-Kalff, M. M. A . Plant Cell Environ. 1997, 20, 449-460. 58. Kaluzna, A . ; Bartosz, G . Biochem. Mol. Biol Int. 1997, 43, 161-171. 59. Lee, H . C.; Toung, Y. P. S.; Tu, Y. S. L . ; Tu, C. P. D . J. Biol. Chem. 1995, 270, 99-109. 60. Hashmi, M.; Dechert, S.; Dekant, W.; Anders, M. W . Chem. Res. Toxicol. 1994, 7, 291-296. 61. Ferguson, G . P. Trends Microbiol. 1999, 7, 242-247. 62. Gisi, D.; Willi, L . ; Traber, H . ; Leisinger, T.; Vuilleumier, S. Appl. Environ. Microbiol 1998, 64, 1194-1202. 63. Mills, J.; Wyborn, N. R.; Greenwood, J. A.; Williams, S. G.; Jones, C. W . Eur. J. Biochem. 1998, 251, 45-53. 64. Salt, D . E.; Smith, R. D . ; Raskin, I. Annu. Rev. Plant Physiol. Plant Mol. Biol. 1998, 49, 643-668.


Bacterial Glutathione - American Chemical Society

Recommend Documents