The crystal structure of a multifunctional protein: Phosphoglucose isomerase/autocrine motility factor/neuroleukin

The crystal structure of a multifunctional protein: Phosphoglucose isomerase/autocrine motility factor/neuroleukin

^*Institute of Molecular Biology, Academia Sinica, Taipei, Taiwan 11529, Republic of China; ^†Graduate Institute of Life Science, National Defense Medical Center, Taipei, Taiwan 11217, Republic of China; ^‡Veterans General Hospital, Taipei, Taiwan 11221, Republic of China; ^§Graduate Institute of Biopharmaceutical Science, National Yang-Ming University, Taipei, Taiwan 11221, Republic of China; and ^¶Graduate Institute of Agricultural Biotechnology, National Chung Hsing University, Taichung, Taiwan 40227, Republic of China

Edited by Robert Huber, Max Planck Institute for Biochemistry, Martinsried, Germany, and approved March 20, 1999 (received for review December 21, 1998)

Abstract

Phosphoglucose isomerase (PGI) plays a central role in both the glycolysis and the gluconeogenesis pathways. We present here the complete crystal structure of PGI from Bacillus stearothermophilus at 2.3-Å resolution. We show that PGI has cell-motility-stimulating activity on mouse colon cancer cells similar to that of endogenous autocrine motility factor (AMF). PGI can also enhance neurite outgrowth on neuronal progenitor cells similar to that observed for neuroleukin. The results confirm that PGI is neuroleukin and AMF. PGI has an open twisted α/β structural motif consisting of two globular domains and two protruding parts. Based on this substrate-free structure, together with the previously published biological, biochemical, and modeling results, we postulate a possible substrate-binding site that is located within the domains’ interface for PGI and AMF. In addition, the structure provides evidence suggesting that the top part of the large domain together with one of the protruding loops might participate in inducing the neurotrophic activity.

Footnotes

↵ ‖ To whom reprint requests should be addressed. e-mbhsiao{at}ccvax.sinica.edu.tw.
This paper was submitted directly (Track II) to the Proceedings Office.
Data deposition: The atomic coordinates have been deposited in the Protein Data Bank, Biology Department, Brookhaven National Laboratory, Upton, NY 11973 (PDB ID code 2PGI).
ABBREVIATIONS:

PGI,

phosphoglucose isomerase;

AMF,

autocrine motility factor;

NLK,

neuroleukin;

MF,

maturation factor;

EGF,

epidermal growth factor