HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS		QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

This Article Full Text Full Text (PDF) All Versions of this Article: ps.041070205v1 14/3/727    most recent Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Lee, J. H. Articles by Jeffery, C. J. Search for Related Content PubMed PubMed Citation Articles by Lee, J. H. Articles by Jeffery, C. J. Social Bookmarking                   What's this?

The crystal structure of rabbit phosphoglucose isomerase complexed with D-sorbitol-6-phosphate, an analog of the open chain form of D-glucose-6-phosphate

Laboratory for Molecular Biology, Department of Biological Sciences, University of Illinois at Chicago, Chicago, Illinois 60607, USA

(RECEIVED September 3, 2004; FINAL REVISION November 5, 2004; ACCEPTED November 8, 2004)

Phosphoglucose isomerase (PGI) catalyzes the isomerization of D-glucose-6-phosphate (G6P) and D-fructose-6-phosphate (F6P) in glycolysis and gluconeogenesis. Analysis of previously reported X-ray crystal structures of PGI without ligand, with the cyclic form of F6P, or with inhibitors that mimic the cis-enediol intermediate led to proposed mechanisms for the ring opening and isomerization steps in the multistep catalytic mechanism. To help complete our model of the overall mechanism, information is needed about the state of PGI between the ring opening and isomerization steps, in other words, a structure of the enzyme complexed with the open form of a substrate or an analog. Here, we report the crystal structure of rabbit PGI complexed with D-sorbitol-6-phosphate (S6P), an analog of the open chain form of G6P, at 2.0 Å resolution. As was seen in the PGI/F6P structure, a helix containing amino acid residues 512–520 is found in the "out" position, which provides sufficient space in the active site for a substrate in its cyclic form and which is probably the location of that helix just after ring opening (or just before ring closure). However, the S6P ligand is in an extended conformation, as was seen previously with ligands that mimic the cis-enediol intermediate. The extended conformation enables the ligand to interact with Glu357, which transfers a proton during the isomerization step. The PGI/S6P structure represents the conformation of the enzyme and substrate between the ring opening (or ring closing) step and the isomerization step and helps to complete the model for PGI’s catalytic mechanism.

Keywords: phosphoglucose isomerase; sorbitol-6-phosphate; catalytic mechanism

Abbreviations: PGI, phosphoglucose isomerase • PDB, Protein Data Bank • 6PGA, 6-phospho-D-gluconate • 5PAH, 5-phospho-D-arabinonhydroxamate • 5PAA, 5-phospho-D-arabinonate • G6P, D-glucose-6-phosphate • F6P, D-fructose-6-phosphate • S6P, D-sorbitol-6-phosphate

Article published online ahead of print. Article and publication date are at http://www.proteinscience.org/cgi/doi/10.1110/ps.041070205.

Reprint requests to: Constance J. Jeffery, Laboratory for Molecular Biology, Department of Biological Sciences, MC567, 900 Ashland Ave., University of Illinois at Chicago, Chicago, IL 60607, USA; e-mail: cjeffery{at}uic.edu; fax: (312) 413-2691.

CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this?

This article has been cited by other articles:

				E. E. Kooijman, D. P. Tieleman, C. Testerink, T. Munnik, D. T. S. Rijkers, K. N. J. Burger, and B. de Kruijff An Electrostatic/Hydrogen Bond Switch as the Basis for the Specific Interaction of Phosphatidic Acid with Proteins J. Biol. Chem., April 13, 2007; 282(15): 11356 - 11364. [Abstract] [Full Text] [PDF]