ENZYMES of Ribose metabolism: structure and mechanism

Sherry L. Mowbray,^a C. Evalena Andersson,^b Annette Roos,^b Torsten Unge ^b and T. Alwyn Jones^b

^aDepartment of Molecular Biosciences, Division of Structural Biology, Swedish University of Agricultural Sciences, BMC, Box 590, SE-751 24 Uppsala, Sweden; ^bDepartment of Cell and Molecular Biology, Uppsala University, BMC, Box 596, S-751 24 Uppsala, Sweden (mowbray@xray.bmc.uu.se)

Although it is well established that ribose is a crucial sugar, its metabolism has only recently been investigated from a structural and mechanistic point of view. Our studies have explored the ribokinase and ribose-5-phosphate isomerases essential for using (and re-cycling) ribose, as well as in its interconversion with other sugars.

Ribokinase was the first example of a new fold since found in related enzymes such as adenosine kinase. Conformational changes associated with ribose binding also are typical of the family[1]. Ribokinase’s activation by a monovalent cation was linked to the formation an anion hole in the active site, the first documented case of allosteric activation of a carbohydrate kinase by an ion[2] Site-directed mutagenesis successfully created an ion-independent version of ribokinase[3].

Ribose-5-phosphate isomerase interconverts ribose-5-phosphate and ribulose-5-phosphate, and is thus an essential enzyme in the pentose phosphate pathway and the Calvin cycle of plants. Two types of unrelated enzyme exist, often within the same organism. The structure of RpiA from E. coli was studied together with the groups of Savchenko (Toronto), Edwards (Toronto) and Joachimiak (Argonne)[4]. This was again a new fold; the structure showed how the ribose ring could be opened to provide the linear form necessary for isomerizaton, as well as identifying the groups needed for binding and catalysis. A second, unrelated type of ribose-5-phosphate isomerase from E. coli (RpiB) was found to have a completely different fold and catalytic mechanism[5]. The enzyme from Mycobacterium tuberculosis has a structure closely related to RpiB, but with a different catalytic mechanism[6]. The three Rpis thus present interesting examples of convergent and divergent evolution.

References

1 Sigrell, J.A., Cameron, A.D., Jones, T.A. & Mowbray, S.L. (1998) Structure 6, 183-193; Sigrell, J.A., Cameron, A.D. and Mowbray, S.L. (1999) J. Mol. Biol. 290, 1009-1018.

2 Andersson, C.E. and Mowbray, S.L. (2002) J. Mol. Biol. 315, 409-19.

3 Andersson, C.E., Roos, A. Unge, T. and Mowbray, S.L. (2003) in preparation.

4 Zhang, R., Andersson, C.E., Savchenko, A., Skarina, T., Evdokimova, E., Beasley, S., Arrowsmith, C.H., Edwards, A.M., Joachimiak, A. and Mowbray, S.L. (2003) Structure 11, 31-42.

5 Zhang, R.-g., Andersson, C.E., Skarina, T., Evdokimova, E., Edwards, A.M., Joachimiak, A., Savchenko, A. & Mowbray, S. L. (2003) J. Mol. Biol. submitted.

6 Roos, A., Andersson, C.E., Joachimiak, A., Unge,, T., Jones, T.A, and Mowbray, S.L. (2003) in preparation.