The Mechanism of Sugar Phosphate Isomerization by Glucosamine 6-phosphate Synthase

Overview

Journal Protein Sci

Specialty Biochemistry

Date 1999 Mar 26

PMID 10091662

Citations 21

Authors

A Teplyakov

G Obmolova

B Badet

Affiliations

Soon will be listed here.

Abstract

Glucosamine 6-phosphate synthase converts fructose-6P into glucosamine-6P or glucose-6P depending on the presence or absence of glutamine. The isomerase activity is associated with a 40-kDa C-terminal domain, which has already been characterized crystallographically. Now the three-dimensional structures of the complexes with the reaction product glucose-6P and with the transition state analog 2-amino-2-deoxyglucitol-6P have been determined. Glucose-6P binds in a cyclic form whereas 2-amino-2-deoxyglucitol-6P is in an extended conformation. The information on ligand-protein interactions observed in the crystal structures together with the isotope exchange and site-directed mutagenesis data allow us to propose a mechanism of the isomerase activity of glucosamine-6P synthase. The sugar phosphate isomerization involves a ring opening step catalyzed by His504 and an enolization step with Glu488 catalyzing the hydrogen transfer from C1 to C2 of the substrate. The enediol intermediate is stabilized by a helix dipole and the epsilon-amino group of Lys603. Lys485 may play a role in deprotonating the hydroxyl O1 of the intermediate.

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References

ZALKIN H . The amidotransferases. Adv Enzymol Relat Areas Mol Biol. 1993; 66:203-309. DOI: 10.1002/9780470123126.ch5. View

ZALKIN H, Smith J . Enzymes utilizing glutamine as an amide donor. Adv Enzymol Relat Areas Mol Biol. 1998; 72:87-144. DOI: 10.1002/9780470123188.ch4. View

Massiere F . The mechanism of glutamine-dependent amidotransferases. Cell Mol Life Sci. 1998; 54(3):205-22. PMC: 11147313. DOI: 10.1007/s000180050145. View

Teplyakov A, Obmolova G, Badet B, Polikarpov I . Involvement of the C terminus in intramolecular nitrogen channeling in glucosamine 6-phosphate synthase: evidence from a 1.6 A crystal structure of the isomerase domain. Structure. 1998; 6(8):1047-55. DOI: 10.1016/s0969-2126(98)00105-1. View

Malaisse-Lagae F, Liemans V, Yaylali B, Sener A, Malaisse W . Phosphoglucoisomerase-catalyzed interconversion of hexose phosphates; comparison with phosphomannoisomerase. Biochim Biophys Acta. 1989; 998(2):118-25. DOI: 10.1016/0167-4838(89)90262-8. View

Rose I . Mechanism of the aldose-ketose isomerase reactions. Adv Enzymol Relat Areas Mol Biol. 1975; 43:491-517. DOI: 10.1002/9780470122884.ch6. View

Nickbarg E, Davenport R, Petsko G, Knowles J . Triosephosphate isomerase: removal of a putatively electrophilic histidine residue results in a subtle change in catalytic mechanism. Biochemistry. 1988; 27(16):5948-60. DOI: 10.1021/bi00416a019. View

Banerjee S, Anderson F, Farber G . The evolution of sugar isomerases. Protein Eng. 1995; 8(12):1189-95. DOI: 10.1093/protein/8.12.1189. View

Golinelli-Pimpaneau B, Badet B . Possible involvement of Lys603 from Escherichia coli glucosamine-6-phosphate synthase in the binding of its substrate fructose 6-phosphate. Eur J Biochem. 1991; 201(1):175-82. DOI: 10.1111/j.1432-1033.1991.tb16271.x. View

10.

Knowles J . Enzyme catalysis: not different, just better. Nature. 1991; 350(6314):121-4. DOI: 10.1038/350121a0. View

11.

Traxinger R, Marshall S . Coordinated regulation of glutamine:fructose-6-phosphate amidotransferase activity by insulin, glucose, and glutamine. Role of hexosamine biosynthesis in enzyme regulation. J Biol Chem. 1991; 266(16):10148-54. View

12.

Collyer C, Blow D . Observations of reaction intermediates and the mechanism of aldose-ketose interconversion by D-xylose isomerase. Proc Natl Acad Sci U S A. 1990; 87(4):1362-6. PMC: 53475. DOI: 10.1073/pnas.87.4.1362. View

13.

Jones T, Zou J, Cowan S, Kjeldgaard M . Improved methods for building protein models in electron density maps and the location of errors in these models. Acta Crystallogr A. 1991; 47 ( Pt 2):110-9. DOI: 10.1107/s0108767390010224. View

14.

Oliva G, Fontes M, Garratt R, Altamirano M, Calcagno M, Horjales E . Structure and catalytic mechanism of glucosamine 6-phosphate deaminase from Escherichia coli at 2.1 A resolution. Structure. 1995; 3(12):1323-32. DOI: 10.1016/s0969-2126(01)00270-2. View

15.

Murshudov G, Vagin A, Dodson E . Refinement of macromolecular structures by the maximum-likelihood method. Acta Crystallogr D Biol Crystallogr. 1997; 53(Pt 3):240-55. DOI: 10.1107/S0907444996012255. View

16.

Obmolova G, Badet B, Teplyakov A . Crystallization and preliminary X-ray analysis of the two domains of glucosamine-6-phosphate synthase from Escherichia coli. J Mol Biol. 1994; 242(5):703-5. DOI: 10.1006/jmbi.1994.1619. View

17.

Denisot M, Le Goffic F, Badet B . Glucosamine-6-phosphate synthase from Escherichia coli yields two proteins upon limited proteolysis: identification of the glutamine amidohydrolase and 2R ketose/aldose isomerase-bearing domains based on their biochemical properties. Arch Biochem Biophys. 1991; 288(1):225-30. DOI: 10.1016/0003-9861(91)90188-o. View

18.

Blacklow S, Knowles J . How can a catalytic lesion be offset? The energetics of two pseudorevertant triosephosphate isomerases. Biochemistry. 1990; 29(17):4099-108. DOI: 10.1021/bi00469a012. View

19.

Lavie A, Allen K, Petsko G, Ringe D . X-ray crystallographic structures of D-xylose isomerase-substrate complexes position the substrate and provide evidence for metal movement during catalysis. Biochemistry. 1994; 33(18):5469-80. DOI: 10.1021/bi00184a016. View

20.

Badet B, Vermoote P, Haumont P, Lederer F, LeGoffic F . Glucosamine synthetase from Escherichia coli: purification, properties, and glutamine-utilizing site location. Biochemistry. 1987; 26(7):1940-8. DOI: 10.1021/bi00381a023. View