1MMX

Crystal structure of galactose mutarotase from Lactococcus lactis complexed with D-fucose

Summary for 1MMX

• Entry DOI: 10.2210/pdb1mmx/pdb
• Related: 1MMU 1MMY 1MMZ 1MN0
• Descriptor: Aldose 1-epimerase, alpha-L-fucopyranose, SODIUM ION, ... (4 entities in total)
• Functional Keywords: epimerase, sugar binding, galactosemia, isomerase
• Biological source: Lactococcus lactis
• Total number of polymer chains: 2
• Total formula weight: 77597.22

Authors

Thoden, J.B.,Kim, J.,Raushel, F.M.,Holden, H.M. (deposition date: 2002-09-04, release date: 2002-09-18, Last modification date: 2024-02-14)

Primary citation

Thoden, J.B.,Kim, J.,Raushel, F.M.,Holden, H.M.
Structural and kinetic studies of sugar binding to galactose mutarotase from Lactococcus lactis.
J.Biol.Chem., 277:45458-45465, 2002

PubMed Abstract: Galactose mutarotase catalyzes the conversion of beta-D-galactose to alpha-D-galactose in the Leloir pathway for galactose metabolism. The high resolution x-ray structure of the dimeric enzyme from Lactococcus lactis was recently solved and shown to be topologically similar to the 18-stranded, anti-parallel beta-motif observed for domain 5 of beta-galactosidase. In addition to determining the overall molecular fold of galactose mutarotase, this initial investigation also provided a detailed description of the electrostatic interactions between the enzyme and its physiologically relevant substrate, galactose. Specifically, the side chains of His-96 and His-170 were shown to be located within hydrogen bonding distance to the C-5 oxygen of the substrate, while the carboxylate of Glu-304 was positioned near the C-1 hydroxyl group of the sugar. On the basis of this initial study, a possible role for Glu-304 as the general acid/base group in catalysis was put forth. Here we describe the combined x-ray crystallographic and kinetic analyses of L. lactis galactose mutarotase complexed with D-glucose, D-fucose, D-quinovose, L-arabinose, or D-xylose. These investigations have revealed that there are several distinct binding modes for these sugars, which are dependent upon the spatial orientation of the C-4 hydroxyl group. In those sugars with the same C-4 hydroxyl group orientation as galactose, their C-1 hydroxyl groups are invariably located near Glu-304. For those sugars, which have the same C-4 hydroxyl group configuration as glucose, the C-1 hydroxyls are typically located near Asp-243. These different binding modes correlate with both the observed kinetic parameters and the presence or absence of a hydrogen bond between the guanidinium group of Arg-71 and the C-4 hydroxyl group of the sugar ligand.

PubMed: 12218067
DOI: 10.1074/jbc.M208395200

Experimental method

X-RAY DIFFRACTION (1.8 Å)