Competitive Inhibitors of Mycobacterium tuberculosis Ribose-5-phosphate Isomerase B Reveal New Information about the Reaction Mechanism

Roos, A.K.; Burgos, Emmanuel S.; Ericsson, Daniel; Salmon, Laurent; Mowbray, Sherry L.

doi:10.1074/jbc.m412018200

Cited by 42 publications

(42 citation statements)

References 28 publications

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“…17) Recently, it has been proposed that the cyclic form (especially, the b form) of R5P is initially docked in the active site of RpiB from Mycobacterium tuberculosis, which is causative of tuberculosis, and transformed to the open-chain form, leading to the isomerization reaction to Ru5P via the high-energy intermediate 1,2-cis-enediolate. 18) A similar hypothesis has been proposed for phosphoglucose isomerase. 19) D-Ribose, tested here, is probably phosphorylated in the larvae, as well as other sugars.…”

Section: Discussionmentioning

confidence: 83%

D-Ribose Competitively Reverses Inhibition by D-Psicose of Larval Growth in Caenorhabditis elegans

Sato

Yokoi

Kurose

et al. 2009

Biological & Pharmaceutical Bulletin

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Certain ketohexose stereoisomers have been shown to exert biological activity. L-Sorbose induces glycolytic limitation in canine erythrocytes, leading to hemolysis.1) Phosphorylation of D-fructose 2) or D-tagatose 3) in the liver causes severe metabolic disturbances, due to the accumulation of phosphorylated intermediates. It was recently shown that, among D-and L-forms of ketohexose stereoisomers (psicose, sorbose, fructose, and tagatose), as well as D-glucose and Dgalactose, the rare sugar D-psicose specifically inhibited the motility, growth, and reproductive maturity of L1 stage Caenorhabditis elegans. 4)D-Psicose was recorded as a constituent moiety of the antibiotic psicofuranine, 5) having marked antibacterial 6) and antitumor 7) activities in vivo, from culture filtrates of Streptomyces hygroscopicus var. decoyicus.8) The furanose form of D-psicose resembles in structure that of D-ribose (Fig. 1). This structural resemblance suggests an antimetabolite mode of action. The purpose of this paper is to identify the biochemical target of D-psicose in larvae of C. elegans by testing compounds for their ability to reverse the inhibitory activity of D-psicose and to propose a possible inhibiton mechanism of D-psicose. L1 and L4 Larvae of C. elegans Standard conditions were used for C. elegans cultivation. 9) A stock culture of the Bristol strain of C. elegans was incubated at 20°C in a liquid growth medium (LGM), i.e., complete S medium supplemented with Escherichia coli strain OP50 (28.6 g wet weight per liter), by shaking for 7 d. Dauer stage larvae, induced by starving the culture for 14 d, were transferred onto 3.5-cm NGM agar plates with E. coli at 20°C and L4 larvae were prepared after 24 h. 10) Eggs were collected by treating eggbearing adults with 5.4% alkaline hypochlorite, followed by shaking the eggs in M9 buffer at 20°C for 22 h to prepare L1 larvae. MATERIALS AND METHODS ChemicalsExperiments Individual three-L1 larva sets were incubated in each of 250-ml hemiellipsoidal wells holding 200 ml of LGM containing D-psicose (111 mM) with and without one of the compounds to be tested for reversing activity at 20°C for 84 h, in accordance with the previous method. 4) L1 larvae were incubated as controls in LGM. Similarly, three-L4 or -L1 larva sets were incubated in LGM (200 ml) with and without D-psicose (167 mM) at 20°C. Eighteen larvae were used at each concentration.Motility, Growth, and Reproductive Parameters Nematode motility is expressed as a motility index, ∑ nN n / ∑ N n 4,11) ; N n is the number of worms showing the movements stated in nϭ3 (fully sinusoidal locomotion movements), nϭ2 (slow movements), nϭ1 (feeble wriggling of the upper or lower part), or nϭ0 (motionlessness, death). The worms in the incubation wells were kept at 4°C for 0.5 h to depress their movements, and pictures were taken with a CCD camera attached to a microscope (Olympus BX51). Body lengths were measured by the previous method, 4) which is virtually

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Section: Discussionmentioning

confidence: 83%

D-Ribose Competitively Reverses Inhibition by D-Psicose of Larval Growth in Caenorhabditis elegans

Sato

Yokoi

Kurose

et al. 2009

Biological & Pharmaceutical Bulletin

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“…5PRA binds with the phosphate group in the same position as for the R5P, with interactions to residues Arg113 and His12 in the A molecule, and Arg137 and Arg141 in the B molecule. The proposed ring-opening catalyst, His102-B, 17 interacts with O4, while O3 makes a hydrogen bond with Asp11-A; both interactions are seen in the other structures. Differences in binding occur at the top of the ligand, where O2 of 5PRA lies in the same position as C1 of the substrate and hydrogen bonds to Glu75-A, C1 of 5PRA points in the same direction as O2 of the substrate, and the carboxylate moiety interacts with Glu75 and backbone nitrogen atoms of the oxyanion hole (Fig.…”

Section: Mtrpib Complex Structuresmentioning

confidence: 99%

“…1). 17 The two structures superimpose with an r.m.s. difference of 0.2 Å when all C α atoms of the 5 protein molecules of the asymmetric unit are aligned.…”

Section: Mtrpib Complex Structuresmentioning

confidence: 99%

“…16 Comparison with the EcRpiB structure (1NN4) 16 indicated that while the two proteins are very similar, some key active site residues are different. X-ray structures of MtRpiB in complex with two substrate analogues (2BES and 2BET) 17 allowed us to assign roles for most of the active site residues in the 5-carbon sugar reaction (Fig. 1).…”

Section: Accepted M Manuscriptmentioning

confidence: 99%

“…17 It was considered likely that RpiB is involved in opening the R5P furanose ring, since only 0.1% of the sugar is in the linear form in solution. 23 We previously proposed that His102 of MtRpiB catalyzes this opening by donating a proton to O4 of the furanose.…”

Section: Ring Openingmentioning

confidence: 99%

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d-Ribose-5-Phosphate Isomerase B from Escherichia coli is Also a Functional d-Allose-6-Phosphate Isomerase, While the Mycobacterium tuberculosis Enzyme is Not

Roos

Mariano

Kowalinski

et al. 2008

Journal of Molecular Biology

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SummaryInterconversion of D-ribose 5-phosphate and D-ribulose 5-phosphate is an important step in the pentose phosphate pathway. Two unrelated enzymes with D-ribose-5-phosphate isomerase activity were first identified in Escherichia coli, RpiA and RpiB. In this organism, the essential 5-carbon sugars were thought to be processed by RpiA, while the primary role of RpiB was suggested instead to be interconversion of the rare 6-carbon sugars, D-allose 6-phosphate and D-allulose 6-phosphate. In Mycobacterium tuberculosis, where only an RpiB is found, the 5-carbon sugars are believed to be the enzyme's primary substrates. Here we present kinetic studies examining the D-allose-6-phosphate isomerase activity of the RpiBs from these two organisms, and show that only the E. coli Keywords: Ribose-5-phosphate isomerase; allose-6-phosphate isomerase; rare sugar; Xray crystallography; Rv2465c. A C C E P T E D M A N U S C R I P T ACCEPTED MANUSCRIPT

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Biological Aspects of Metal Enolates

Ming

2010

Patai's Chemistry of Functional Groups

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Competitive Inhibitors of Mycobacterium tuberculosis Ribose-5-phosphate Isomerase B Reveal New Information about the Reaction Mechanism

Abstract: Ribose-5-phosphate isomerases (Rpi 1 ; EC 5.3.1.6) catalyze the conversion of ribose 5-phosphate (R5P) to ribulose-5-phosphate (Ru5P) and vice versa (Fig.

Cited by 42 publications

References 28 publications

D-Ribose Competitively Reverses Inhibition by D-Psicose of Larval Growth in Caenorhabditis elegans

D-Ribose Competitively Reverses Inhibition by D-Psicose of Larval Growth in Caenorhabditis elegans

d-Ribose-5-Phosphate Isomerase B from Escherichia coli is Also a Functional d-Allose-6-Phosphate Isomerase, While the Mycobacterium tuberculosis Enzyme is Not

Biological Aspects of Metal Enolates

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