Trends in Glycoscience and Glycotechnology 30(172): SE41-SE50
(2018)© 2018 FCCA (Forum: Carbohydrates Coming of Age)SE41
Trends in Glycoscience and Glycotechnology Vol. 30 No. 172
(January–May 2018) pp. SE41–SE50
Three-Dimensional Structures of Galectins
Shigehiro Kamitori Life Science Research Center and Faculty of
Medicine, Kagawa University, 1750–1, Ikenobe, Miki-cho, Kita-gun,
Kagawa 761–0793, Japan
FAX: +81–87–891–2421, E-mail:
[email protected]
(Received on August 18, 2017, accepted on October 5, 2017)
Key Words: carbohydrate recognition domain, oligosaccharide,
prototype galectin, tandem-repeat type galectin, X-ray crystal
structure
Abstract The galectins are a family of β-galactoside-specific
animal lectins that contain a conserved carbohydrate recognition
domain
(CRD) with approximately 140 amino acid residues. There are 14
members in the mammalian galectin family (galectin-1–10, and 11–
15), and they have different specificities for oligosaccharides.
X-ray structures of the galectin CRD in complexes with oligosaccha-
rides have provided important clues about the
oligosaccharide-recognition mechanisms of galectins giving the
different specificities. Galectin is divalent in glycan binding due
to the association of two CRDs that crosslink with
oligosaccharides. The spatial arrange- ment of the two CRDs is very
important for elucidating the biological functions of galectins.
Several different spatial arrangements of CRDs are found in X-ray
structures of galectins. I herein examined the three-dimensional
structures of galectins relevant for biological functions, based on
the protein–ligand interactions related with
oligosaccharide-specificity, the cross-linking structure by
galectin and oligosaccharides, and the spatial arrangements of
CRDs.
A. Introduction The galectins are a family of
β-galactoside-specific animal
lectins that contain a conserved carbohydrate recognition domain
(CRD) with approximately 140 amino acid residues, and have at-
tracted much attention as novel regulators of the immune system (1,
2). There are 14 members in the galectin family (galectin-1–10, and
12–15), which are classified into three subtypes based on
structure. The prototypes (galectin-1, 2, 5, 7, 10, 13, 14 and 15)
have a single CRD. The chimera type (galectin-3) has a single CRD
and a non-lectin N-terminal domain. The tandem-repeat types
(galectin-4, 6, 8, 9, and 12) have two different CRDs in the N- and
C-terminal regions (N-CRD and C-CRD) that are joined by a linker
peptide (Fig. 1A). The prototype galectins mostly form homo-dimers,
and the chimera type galectin is expected to form an oligomer based
on its non-lectin N-terminal domain. Thus, ga- lectins are divalent
and/or multivalent in glycan binding. The most well-characterized
role of galectins is crosslinking with oligosac- charides in the
extracellular space, which is involved in cell–cell and cell–matrix
interactions. Recently, additional roles of galectins in the
cytosol have attracted interest (3, 4).
Galectin CRDs have different specificities for oligosaccha- rides.
The N-CRD of galectin-8 (galectin-8_N-CRD) exhibits a strong
affinity for α(2-3)-sialylated oligosaccharides, but the C- CRD
does not. The N-CRD of galectin-9 (galectin-9_N-CRD) has high
affinity for oligolactosamines with a linear structure, but the
C-CRD does not. Both the galectin-9_N-CRD and C-CRD have high
affinities for N-glycan-type branched oligosaccharides (bi-
anntenary oligosaccharides) (5). Many X-ray structures of galectin
CRDs in complexes with oligosaccharides have been deposited into
PDB (6), and have provided important clues about the oligo-
saccharide-recognition mechanisms of galectins giving the differ-
ent specificities (7–18). Selected oligosaccharides and a synthetic
ligand used in structural studies of galectin CRDs are listed in
Fig. 1B with their abbreviations.
Most of the reported X-ray structures of galectins contained only a
single type of CRD. The homo-dimer structures of the prototype
galectins were found to show the spatial arrangements of CRDs.
However, there was no information about the spatial ar- rangement
of the CRDs of chimera type and tandem-repeat type galectins.
Tandem-repeat type galectins are inherently divalent in glycan
binding with different specificities, and structural informa- tion
about the spatial arrangement of the two CRDs is very impor- tant
for elucidating their biological functions. Tandem-repeat type
galectins are sensitive to proteases due to the long linker. To
carry out X-ray crystal structure determinations of tandem-repeat
type galectins with two CRDs, the galectins with a short linker(19)
and/ or the protease-resistant mutant forms with a modified linker
pep- tide were used (20–22).
In this review, I examined three-dimensional structures of
galectins based on the protein–ligand interactions related with
oligosaccharide-specificity, the cross-linking structure by
galectin and oligosaccharides, and the spatial arrangements of CRDs
of the prototype and tandem-repeat type galectins. Galectin-1, 2,
7, 8, 9, 10 stand for human galectin-1, 2, 7, 8, 9, 10,
respectively (unless stated otherwise). Figures 2, 3, 4, 5 were
drawn with the program PyMOL(23).
B. Three-Dimensional Structure of Galectin CRD The overall
structure of galectin-9_C-CRD in complex with
LacNAc (galectin-9_C-CRD/LacNAc (PDB ID: 3NV2)) (17) is
MINIREVIEW doi: 10.4052/tigg.1731.1SE(Article for special issue on
Galectins)
© 2018 FCCA (Forum: Carbohydrates Coming of Age) SE42
Fig. 1. Three subtypes of galectins and ligands used in structural
studies of galectins. (A) Schematic diagrams showing the three
subtypes of galectins are illustrated. (B) Chemical structures of
oligosaccharides and a synthetic ligand are illustrated with their
abbreviations.
© 2018 FCCA (Forum: Carbohydrates Coming of Age)SE43
shown in Fig. 2A. The galectin-9_C-CRD adopts a β-sandwich
structure formed by two anti-parallel β-sheets consisting of six
(S1–S6) and five (F1–F5) β-strands, respectively. The strand S6 is
divided into two strands (S6a and S6b). A short helix (H1) exists
between F5 and S2. The carbohydrate-binding sites are exposed to
the solvent-accessible surfaces of the molecule, and a LacNAc binds
to the concave surfaces formed by S3, S4, S5 and S6, via
non-reducing and reducing ends located at S3 to S6. The overall
structure is well conserved among galectin CRDs, and can be
represented by a tetragonal prism. For clarity, the face, back,
top, bottom and sides of the CRD are defined as in Fig. 2A (right).
The
carbohydrate-binding site is on the face of the CRD, and the oppo-
site side is the back. The short helix (H1) is on the bottom and
the opposite side is the top. The β-strand of S1 is on the right
side and S6 is on the left side.
Three structures of galectin CRDs in complexes with oligo-
saccharides are shown in Fig. 2B. Sugar units of the bound oligo-
saccharides are numbered −1, +1, and +2, from the non-reducing end
to reducing end (Fig. 1B). Gal+1 occupies the same position in each
complex.
In galectin-9_C-CRD/LacNAc (3NV2) (17), the galactose moiety
(Gal+1) forms stacking interactions with Trp255, and forms
Fig. 2. X-ray structures of galectin CRDs with the bound
oligosaccharides. (A) Overall structure of galectin-9_C-CRD/LacNAc
(3NV2) is illustrated as viewed from the face (left) and the left
side (middle). The β-sheet on the back of the CRD is shown in a
dark color, and a short helix (H1) is shown in red. A schematic
diagram of tetragonal prisms showing the CRD is illustrated
(right). The back, bottom and right sides of tetragonal prisms are
shown in gray. (B) Galectin-9_C-CRD/LacNAc (3NV2) (left),
Galectin-8_N-CRD/SiaLacNAc (3VKO) (middle) and Galectin-9_N-CRD/
LN3 (2ZHM) (right) are illustrated with the protein–ligand
interactions.
© 2018 FCCA (Forum: Carbohydrates Coming of Age) SE44
six hydrogen bonds with the protein: O4-His235, O4-Asn237,
O4-Arg239, O5-Arg239, O6-Asn248 and O6-Glu258. The axial
conformation of the O4 of Gal+1 is strictly recognized by three
hy-
drogen bonds from His235, Asn237 and Arg239. The glucosamine moiety
(GlcNAc+2) forms hydrogen bonds with the protein by O3: O3-Arg239,
O3-Glu258, and O3-Arg260. As Arg239 and Glu258
Fig. 3. Cross-linking structures by galectins and oligosaccharides.
(A) Bovine galectin-1/BIOS (1SLA) is illustrated. The S4–S5 loop is
shown in red. A schematic diagram showing the cross-linked
structure is illustrated (right). (B) Galectin-9_C-CRD/BIOS (3NV3)
is illustrated. The modeled GlcNAc+5 and Man+4 are shown in blue.
(C) Galectin-7/D2 (4UW5) is illustrated.
© 2018 FCCA (Forum: Carbohydrates Coming of Age)SE45
form bifurcated hydrogen bonds with both Gal+1 and GlcNAc+2, they
efficiently recognize the β (1-4) glycoside bond of LacNAc. The
protein–ligand interactions found in galectin-9_C-CRD/ LacNAc are
conserved in galectin CRD/oligosaccharide complex structures.
In galectin-8_N-CRD/SiaLacNAc (3VKO) (21), in addition to the
conserved protein–ligand interactions, Arg59 forms ef- ficient
salt–bridge interactions with the carboxyl group of Sia−1, and
Gln47 and Trp86 hold the carboxyl group from both sides via
hydrogen bonds. Arg59 is unique to galectin-8_N-CRD, and may be
responsible for the strong affinity for α(2-3)-sialylated oligosac-
charides.
In galectin-9_N-CRD/LN3 (2ZHM) (16), the bound LN3 has a linear
structure which enables GlcNAc−1 to form a hydrogen bond with
Asn48. Furthermore, Ala46, which is unique to galec- tin-9_N-CRD,
is proposed to be one of the residues responsible for the high
affinity for oligolactosamines (13). This is because an amino acid
residue with bulky side chain group at the position of Ala46
(His223 in galectin-9_C-CRD and/or Gln47 in galectin-8_ N-CRD)
causes steric hindrance with GlcNAc−1 of LN3.
C. Cross-Linking Structure by Galectin and Oligosac- charides
Galectin crosslinks with oligosaccharides, and the N-glycan-
Fig. 4. Spatial arrangements of CRDs of prototype galectins. (A)
The homo-dimer of galectin-1/LacNAc (1W6P) is illustrated with a
sche- matic diagram showing the spatial arrangement of the two
CRDs. The β-sheet on the back of the CRD is shown in a dark color.
(B) The homo-dimer of galectin-7/Gal (2GAL) is illustrated. (C) The
homo-dimer of galectin-10/Man (1QKQ) is illustrated. (D) The
homo-tetramer of Xenopus laevis skin galectin Va (3WUC) is
illustrated.
© 2018 FCCA (Forum: Carbohydrates Coming of Age) SE46
Fig. 5. Spatial arrangements of CRDs of tandem-repeat type
galectins. (A) Galectin-9Null_R221S/Lac (3WV6) is illustrated. The
N-CRD, C-CRD and linker are shown in blue, pink and yellow,
respectively, and the β-sheet on the back of the CRD is shown in a
dark color. (B) Porcine Ad- enovirus Type 4 galectin domain/Lac
(2WSV) is illustrated. The C-CRD is shown in salmon pink. A LN3
molecule binding to the groove (2WT2) is superimposed. (C)
Galectin-8Null/SiaLac/Lac (3VKM) is illustrated. The C-CRD is shown
in green. (D) The homo-dimer of galectin-8Null/SiaLac/ Lac is
illustrated. (E) Galectin-8Null/NDP52-peptide (4HAN) is
illustrated. (F) The homo-dimer of galectin-8Null/NDP52-peptide is
illustrated.
© 2018 FCCA (Forum: Carbohydrates Coming of Age)SE47
type branched oligosaccharide is also able to crosslink with galec-
tins.
The X-ray structure of bovine galectin-1 in complex with
BIOS was reported with three crystal forms, hexagonal, trigonal and
monoclinic, and the structure in the hexagonal form (bovine
galectin-1/BIOS (1SLA)) is shown in Fig. 3A (7). In this
structure,
Table 1. Geometrical parameters for spatial arrangements of the two
CRDs.
CRD orientation Solvent-accessible
Solvent-accessible surface area of the
2nd CRD (2)
solvent-accessible surface area (%)
Distance between carbohydrate
recognition sitesa ()
Interface area (2)
(Mol-A) 6784
(Mol-A) 7077
(Mol-A) 6773
Side-to-side 581 6840
(5GM0) Back-to-back
Face-to-face 671 7287
(3WV6) Back-to-back
Back-to-back 417 7011
(C-CRD, Mol-A) 7297
Galectin-8Null/NDP52- peptide (4HAN)
Back-to-side 391 8636
(N-CRD, Mol-A) 7252
(N-CRD, Mol-B) 8575 10.4 —
a The distance is defined as the distance between the O4 atoms of
Gal+1 (Man+1 for galectin-10/Man) of the bound ligand molecules at
the two CRDs. In rat galectin-5 and galectin-8Null/NDP52-peptide
(4HAN), there is no oligosaccharide to bind.
© 2018 FCCA (Forum: Carbohydrates Coming of Age) SE48
the S4–S5 loop (shown in red), including His52 and Gly53, over-
laps BIOS, creating a deep carbohydrate-binding site. His52 and
Trp68 sandwich Gal+1 and GlcNAc+2 to fix their positions, and Gly53
efficiently forms van der Waals contacts with Man3+ and
Man+4.
The structure of galectin-9_C-CRD/BIOS (3NV3) is shown in Fig. 3B
(17). As the electron density of Man+4 and GlcNAc+5 was invisible
due to high disorder, they were modeled. The S4–S5 loop, including
Asp241 and Glu242, is not directed toward BIOS, creating a shallow
carbohydrate-binding site. The entrance for the ligand-binding of
galectin-9_C-CRD is widely opened, and Man+3 and Man+4 of BIOS are
free from the protein without any direct interactions.
Galectin-9_N-CRD also has a similar S4–S5 loop structure with
galectin-9_C-CRD, creating a shallow carbohydrate- binding
site.
Bovine galectin-1 with a deep carbohydrate-binding site can form
stable protein–ligand complexes of low structural energy through
many attractive interactions, compared with galectin-9 CRDs.
However, the conformation of the bound oligosaccharide may be
restricted by strong protein–ligand interactions. Indeed, the
extended conformation of the bound oligosaccharides was only found
in X-ray structures of bovine galectin-1/BIOS in three crys- tal
forms (Fig. 3A, right). In the case of galectin-9 CRDs, protein–
ligand interactions were limited to Gal+1 and GlcNAc+2, and other
sugar units were free from the protein, meaning that galectin-9
CRDs recognizes the antennae of a branched oligossacharide in
several conformations (Fig. 3B, right). In galectin-9 CRDs, the
less structural energy in the formation of a protein–ligand complex
is probably compensated for by the ability to accept branched
oligos- sacharides in different conformations. This may be one of
the rea- sons why galectin-9_N-CRD and C-CRD have high affinities
for N-glycan-type branched oligossacharides (17).
The X-ray structure of galectin-7 in complex with synthetic
galactose-based dendron with three arms (galectin-7/D2 (4UW5)) was
reported (13). In this structure, each galactose-terminus of the
three arms of D2 is recognized by one galectin-7 molecule (Fig.
3C). The prototype galectin-7 forms a homo-dimer. Thus, D2 links
three molecules of galectin-7, and the dimer partner of these
galec- tin-7 molecules binds to another D2, likely forming
supramolecu- lar assemblies with a lattice structure. (Fig. 3C,
right) (13, 24).
D. Spatial Arrangements of CRDs of Prototype Galectins In the X-ray
structures of prototype galectins, three spatial
arrangements of CRDs were found, the side-to-side, the back-to-
back, and the face-to-face orientations, to form a homo-dimer and a
homo-tetramer. Figure 4 shows their structures with schematic
diagrams. Geometrical parameters for spatial arrangements of
CRDs are listed in Table 1. Galectin-1 (1W6P) (8) and galectin-2
(1HLC) (9) form a
homo-dimer with a 2-fold symmetry, making contacts between the
right sides of the CRDs (the side-to-side orientation) (Fig. 4A).
On dimerization, pairs of the same β-sheets are connected to give
two large antiparallel β-sheets with an interface area of 620 2.
Two carbohydrate-binding sites are located on the same side of the
homo-dimer and separated from each other by 41 .
Galectin-7 (2GAL) (12) forms a homo-dimer with a 2-fold symmetry,
making contact between the β-sheets on the back (the back-to-back
orientation) with an interface area of 768 2. Two
carbohydrate-binding sites are located at both ends of the homo-
dimer with a distance of 50 , facing opposite each other.
In the X-ray structure of galectin-10 (1QKQ) (18), CRDs re- lated
by a crystallographic 2-fold symmetry are associated in the
face-to-face orientation with an interface area of 821 2 (Fig. 4C).
The distance between the two carbohydrate-binding sites is 17 .
However, it is still unclear whether galectin-10 forms a homo-
dimer in the face-to-face orientation in solution. The X-ray struc-
ture of the rat galectin-5 (5JPG), recently released on PDB, was a
homo-dimer in the face-to-face orientation.
The Xenopus laevis skin galectin Va (3WUC) (25) and the marine
sponge (Cinachyrella sp.) galectin (4AGR) (26) form homo-tetramers
in which two homo-dimers in the side-to-side ori- entation are
associated in the back-to-back orientation (Fig. 4D). As four
carbohydrate-binding sites are located on the solvent-ac- cessible
surface of the homo-tetramer, these galectins are expected to be
tetravalent in glycan binding.
E. Spatial Arrangements of CRDs of Tandem-Repeat Type
Galectins
In the X-ray structures of tandem-repeat type galectins having two
CRDs, three spatial arrangements of CRDs were found, the
back-to-back, the face-to-face, and the back-to-side orientations,
as shown in Fig. 5.
In the X-ray structure of the protease-resistant mutant form of
galectin-9 with a short linker of 19 amino acid residues and the
replacement of Arg221 by Ser (galectin-9Null_R221S (3WV6)) (22),
the two CRDs are associated, making contact between the β-sheets on
the back with many hydrophobic interactions (the back-to-back
orientation) (Fig. 5A). Compared with the homo- dimer of galectin-7
in the back-to-back orientation, the two CRDs of
galectin-9Null_R221S are distorted from the 2-fold symmetry, giving
a small interface area of 632 2 and a distance between two
carbohydrate-binding sites of 47 (Table 1). The back surfaces of
the galectin-9 CRDs exhibited high hydrophobicity with low
solubility (27). These hydrophobic residues are buried
between
© 2018 FCCA (Forum: Carbohydrates Coming of Age)SE49
the two CRDs in the back-to-back orientation, giving a favorable
structure to the protein in solution. The tandem-repeat type Toxas-
caris leonina galectin (5GM0) (19) with 34% amino acid sequence
similarity with galectin-9 also adopts the back-to-back orientation
with hydrophobic interactions as found in
galectin-9Null_R221S.
The Porcine Adenovirus Type 4 has a fiber protein contain- ing a
tandem-repeat type galectin domain. In the X-ray structure of this
galectin domain (2WSV) (28), the face-to-face orientation was
observed (Fig. 5B). Compared with the homo-dimer of ga- lectin-10
in the face-to-face orientation, the two CRDs are largely distorted
from the 2-fold symmetry with a small interface area of 671 2, to
form the deep groove for ligand-binding between the two CRDs. Two
carbohydrate-binding sites approach the distance of 12 , exposing
the solvent-accessible surface. As a long oligo- lactosamine (LN3)
was found to bind the groove between the two CRDs (2WT2), the
face-to-face orientation of the two CRDs was proposed to allow both
CRDs to interact with the same oligosac- charide in the recognition
of complex sugars (28).
In the X-ray structure of the protease-resistant mutant form of
galectin-8 with a short linker of 7 amino acid residues, in which
the N-CRD recognized SiaLac and the C-CRD recognized Lac,
(galectin-8Null/SiaLac/Lac (3VKM)) (21), the two CRDs are as-
sociated in the back-to-side orientation (Fig. 5C). The N-CRD of
G8Null has two additional β-strands at the N-terminal site, F01N
and F02N, and F01N interacts with S1C, to participate in a β-sheet
on the face of C-CRD, giving the back-to-side orientation. The car-
bohydrate-binding sites make a right angle with each other at a
dis- tance of 55 . In crystal, two molecules of galectin-8Null
possibly form a dimer, in which the β-sheets on the back of the
C-CRDs face each other to form an interface (the back-to-back
orienta- tion) (Fig. 5D). Four carbohydrate-binding sites are
located on the solvent-accessible surface of the dimer. The
formation of dimeric species of galectin-8 was reported to be
related with its biological function (29). The back-to-side
orientation found in galectin-8Null may be favorable for forming a
dimeric structure.
Galectin-8 was reported to activate antibacterial autophagy by
interacting with the autophagic receptor NDP52 (30), and the X-ray
structure of galectin-8Null in complex with the peptide frag- ment
of NDP52 (galectin-8Null/NDP52-peptide (4HAN)) was reported (31).
These results clearly demonstrate the roles of galec- tin-8 in the
cytosol. In the galectin-8Null/NDP52-peptide, the two CRDs are
associated in the back-to-side orientation, and an addi- tional
β-strand, F0N, interacts with F1C, to participate in a β-sheet on
the back of C-CRD (Fig. 5E). The additional β-strand F0N also
interacts with that of another molecule to form a dimer, making
contact between the β-sheets on the back of the N-CRDs (the back-
to-back orientation) (Fig. 5F). The two C-CRDs recognize the
NDP52-peptides on the back side. Unexpectedly, an NAD from the
crystallization solution was located at one of the carbohydrate-
binding sites (N-CRD of Mol-A).
Galectin-8 may form two types of dimeric structures by mak- ing
contact between N-CRDs or between C-CRDs. In both forms, four
carbohydrate-binding sites are located on the solvent-accessi- ble
surface of the dimer, to be tetravalent in glycan binding.
F. Conclusion Galectin CRDs recognize the β-galactoside moiety
through
protein–ligand interactions by the conserved galectin signature
amino acids. Each galectin CRD exhibits particular preference of
oligosaccharide-binding by unique amino acid residues on each
galectin CRD such as Arg59 of galectin-8_N-CRD and Ala46 of
galectin-9_N-CRD (Fig. 2B). The structural comparison between
bovine galectin-1/BIOS and galectin-9_C-CRD/BIOS suggested that the
shallow carbohydrate-binding site of galectin-9 CRDs is related
with the high affinity for N-glycan-type branched oligossa-
charides (Figs. 3A, B).
The spatial arrangements of the prototype galectins are sym- metric
(Fig. 4), whereas those of the tandem-repeat type galectins are
distorted from the symmetry with less interactions between CRDs
(Fig. 5 and Table 1). Tandem-repeat type galectins with a linker
may flexibly change the spatial arrangements of their two CDRs
depending on their biological roles (Fig. 3B, right).
The structure of galectin-7/D2 suggested that galectin-7 and the
ligand with three arms form supramolecular assemblies with a
lattice structure (Fig. 3C). The Xenopus laevis skin galectin Va
(Fig. 4D) and galectin-8 (Figs. 5D, F) may be tetravalent in glycan
binding. Furthermore, the back of galectin-8_C-CRD targets the
peptide ligand (Figs. 5E, F). It will be very interesting to
elucidate the unknown molecular mechanisms underlying the
biological functions of galectins.
Acknowledgments The author thanks Dr. Hiromi Yoshida, Dr. Nozomu
Nishi,
Dr. Shin-ichi Nakakita, and Dr. Yasuhiro Nonaka for their useful
discussions and critical reading of the manuscript. The research
performed by the author et al. was supported in part by Grants-in-
Aid for Scientific Research (23370054) from the Japan Society for
the Promotion of Science (JSPS), and the fund for Characteristic
Prior Research from Kagawa University.
Abbreviations CRD — carbohydrate recognition domain N-CRD —
N-terminal CRD C-CRD — C-terminal CRD
© 2018 FCCA (Forum: Carbohydrates Coming of Age) SE50
galectin-8_N-CRD — N-CRD of galectin-8 galectin-9_N-CRD — N-CRD of
galectin-9 galectin-9_C-CRD — C-CRD of galectin-9 Lac — lactose
LacNAc — N-acetyllactosamine
SiaLac — α (2-3)-sialyllactose SiaLacNAc — α
(2-3)-N-acetylsialyllactosamine LN3 — tri(N-acetyllactosamine) BIOS
— biantennary oligosaccharide D2 — synthetic galactose-based
dendron
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Shigehiro Kamitori: Graduated from Osaka City University in 1984,
and received a Ph.D. in chemistry from the graduate school of Osaka
City University in 1989. He worked as a research associate at Kyowa
Hakko Kogyo Co., Ltd. (1989–1991), as a postdoctoral fellow at the
University of Kansas (1991–1994), and as an associate professor at
the Tokyo University of Agriculture and Technology (1994–2004), and
became a professor at the Life Science Research Center and Faculty
of Medicine, Kagawa University since 2004. His current research
interests are the structure–function relationship of
carbohydrate-binding proteins and the catalytic reaction mechanisms
of sugar isomerases, as deduced from X-ray structures.
Information of the Authors