5 -Methylthioadenosine nucleosidase

J. A. Gutierrez, T. Crowder, A. Rinaldo-Matthis, M.-C. Ho, S. C. Almo, and V. L. Schramm, Transition state analogs of 5 -methylthioadenosine nucleosidase disrupt quorum sensing, Nat. Chem. Biol., 5 (2009) 251-257. 

Kushad, M.M. Richardson, D.G. Ferro, A.J. 5 -Methylthioadenosine nucleosidase and 5-methylthioribose kinase activities and ethylene production during tomato fruit development and ripening. Plant Physiol., 79, 525-529 (1985)... 

The synthesis of 964 was achieved by coupling 6-chloropurine and 4-methylthiobutan-l-ol (962) under the influence of DEAD/PhaP to give 963, followed by ammonolysis to 964 [93JCS(P1)1109], It was a potent inhibitor of the enzyme methylthioadenosine nucleosidase. 

Allart B, Gatel M, Guillerm D, Guillerm G (1998) The catalytic mechanism of adenosylho-mocysteine/methylthioadenosine nucleosidase from Escherichia coli. Chemical evidence for a transition state with substantial oxocarbenium character. Eur J Biochtan 256 155-162... 

Figure 7-11. 5 -p-Cl-phenylthio-DADMe-Immucillin-A is a femtomolar transition state analogue for E.coli 5 -methylthioadenosine/S-adenosylhomocysteine nucleosidase (MTAN). Initial (Kj) and equilibrium (Kf) dissociation constant are shown... 

Singh V, Evans GB, Lenz DH, Mason JM, Clinch K, Mee S, Painter GF, Tyler PC, Furneaux RH, Lee IE, Howell PL, Schramm VL (2005) Femtomolar transition state analogue inhibitors of 5 -methylthioadenosine/S-adenosylhomocysteine nucleosidase from Escherichia coli. J. Biol. Chem. 280 18265-18273... 

Scheme 6 S -Methylthioadenosine/5-adenosylhomocysteine nucleosidase (MTAN)-catalyzed hydrolysis of S -methylthioadenosine (MTA) to adenine and S-methylthio-D-ribose (MTR).

FIG. 55 Methionine salvage pathway via 5 -methylthioadenosine (MTA). 1, MTA phosphorylase 2, MTA nucleosidase 3, 5-methylthioritese kinase. 

Cornell, K.A. Winter, R.W. Tower, P.A. Riscoe, M.K. Affinity purification of 5-methylthioribose kinase and 5-methylthioadenosine/S-adenosylhomocys-teine nucleosidase from Klebsiella pneumoniae [corrected]. Biochem. J., 317, 285-290 (1996)... 

Fig, 7. Pathways for the metabolism of methionine to 5 -methylthioadenosine (MTA) and recycling of MTA to methionine. Methionine can serve as a carbon source for the synthesis of polyamines and, in some tissues, ethylene. 5 -Methylthioadenosine is a product of both processes. Only the methylthio group of methionine is recycled, the C4 moiety for the resynthesis of methionine being derived from the ribosyl moiety of ATP. The enzymes involved are (1) SAM synthetase, (2) SAM decarboxylase, (3) various C3 transfer enzymes of polyamine biosynthesis, (4) MTA nucleosidase, (5) methylthioribose kinase, (6) three( ) uncharacterized enzymes, (7) aminotransferase, and (8) aminocyciopropane carboxylate synthase. 

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