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PDBsum entry 2jkp
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* Residue conservation analysis
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Enzyme class:
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E.C.3.2.1.3
- glucan 1,4-alpha-glucosidase.
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Reaction:
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Hydrolysis of terminal 1,4-linked alpha-D-glucose residues successively from non-reducing ends of the chains with release of beta-D-glucose.
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DOI no:
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Chem Biol
15:1058-1067
(2008)
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PubMed id:
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Divergence of catalytic mechanism within a glycosidase family provides insight into evolution of carbohydrate metabolism by human gut flora.
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T.M.Gloster,
J.P.Turkenburg,
J.R.Potts,
B.Henrissat,
G.J.Davies.
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ABSTRACT
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Enzymatic cleavage of the glycosidic bond yields products in which the anomeric
configuration is either retained or inverted. Each mechanism reflects the
dispositions of the enzyme functional groups; a facet of which is essentially
conserved in 113 glycoside hydrolase (GH) families. We show that family GH97 has
diverged significantly, as it contains both inverting and retaining
alpha-glycosidases. This reflects evolution of the active center; a glutamate
acts as a general base in inverting members, exemplified by Bacteroides
thetaiotaomicron alpha-glucosidase BtGH97a, whereas an aspartate likely acts as
a nucleophile in retaining members. The structure of BtGH97a and its complexes
with inhibitors, coupled to kinetic analysis of active-site variants, reveals an
unusual calcium ion dependence. 1H NMR analysis shows an inversion mechanism for
BtGH97a, whereas another GH97 enzyme from B. thetaiotaomicron, BtGH97b,
functions as a retaining alpha-galactosidase.
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Selected figure(s)
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Figure 1.
GH Mechanisms and [alpha]-Glucosidase Inhibitors (A and B)
Hydrolysis with (A) inversion and (B) retention of anomeric
configuration. (C) Inhibitors deoxynojirimycin (1),
castanospermine (2), and acarbose (3). Chem Biol. 2008 October
20; 15(10-3): 1058–1067. doi: 10.1016/j.chembiol.2008.09.005.
Copyright [copyright] 2008 Elsevier Ltd.
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Figure 2.
Structural Insights into BtGH97a (A) Divergent stereo ribbon
representation of BtGH97a; the N-terminal domain is in red, the
core ([beta]/[alpha])[8] domain in yellow, and the C-terminal
domain in blue. (B and C) Ball-and-stick representation of
BtGH97a in complex with (B) 1 and (C) 2; observed electron
density for the maximum likelihood weighted 2F[obs] [minus sign]
F[calc] map is contoured at 1[sigma]. The purple spheres
represent calcium ions. (D) Ball-and-stick representation of the
active-site overlap between BtGH97a and a GH27 enzyme (PDB ID
code 1UAS). Figures were drawn using BOBSCRIPT (Esnouf, 1997).
(E) Interactions between BtGH97 and 1. Chem Biol. 2008 October
20; 15(10-3): 1058–1067. doi: 10.1016/j.chembiol.2008.09.005.
Copyright [copyright] 2008 Elsevier Ltd.
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The above figures are
reprinted
from an Open Access publication published by Cell Press:
Chem Biol
(2008,
15,
1058-1067)
copyright 2008.
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Figures were
selected
by an automated process.
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Literature references that cite this PDB file's key reference
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PubMed id
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Reference
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M.Gabriško,
and
S.Janeček
(2011).
Characterization of maltase clusters in the genus Drosophila.
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J Mol Evol,
72,
104-118.
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M.N.Gandy,
A.W.Debowski,
and
K.A.Stubbs
(2011).
A general method for affinity-based proteomic profiling of exo-α-glycosidases.
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Chem Commun (Camb),
47,
5037-5039.
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A.Lammerts van Bueren,
S.D.Popat,
C.H.Lin,
and
G.J.Davies
(2010).
Structural and thermodynamic analyses of α-L-fucosidase inhibitors.
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Chembiochem,
11,
1971-1974.
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PDB codes:
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A.P.Yeh,
P.Abdubek,
T.Astakhova,
H.L.Axelrod,
C.Bakolitsa,
X.Cai,
D.Carlton,
C.Chen,
H.J.Chiu,
M.Chiu,
T.Clayton,
D.Das,
M.C.Deller,
L.Duan,
K.Ellrott,
C.L.Farr,
J.Feuerhelm,
J.C.Grant,
A.Grzechnik,
G.W.Han,
L.Jaroszewski,
K.K.Jin,
H.E.Klock,
M.W.Knuth,
P.Kozbial,
S.S.Krishna,
A.Kumar,
W.W.Lam,
D.Marciano,
D.McMullan,
M.D.Miller,
A.T.Morse,
E.Nigoghossian,
A.Nopakun,
L.Okach,
C.Puckett,
R.Reyes,
H.J.Tien,
C.B.Trame,
H.van den Bedem,
D.Weekes,
T.Wooten,
Q.Xu,
K.O.Hodgson,
J.Wooley,
M.A.Elsliger,
A.M.Deacon,
A.Godzik,
S.A.Lesley,
and
I.A.Wilson
(2010).
Structure of Bacteroides thetaiotaomicron BT2081 at 2.05 Å resolution: the first structural representative of a new protein family that may play a role in carbohydrate metabolism.
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Acta Crystallogr Sect F Struct Biol Cryst Commun,
66,
1287-1296.
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PDB code:
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P.J.Turnbaugh,
B.Henrissat,
and
J.I.Gordon
(2010).
Viewing the human microbiome through three-dimensional glasses: integrating structural and functional studies to better define the properties of myriad carbohydrate-active enzymes.
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Acta Crystallogr Sect F Struct Biol Cryst Commun,
66,
1261-1264.
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T.M.Gloster,
and
G.J.Davies
(2010).
Glycosidase inhibition: assessing mimicry of the transition state.
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Org Biomol Chem,
8,
305-320.
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The most recent references are shown first.
Citation data come partly from CiteXplore and partly
from an automated harvesting procedure. Note that this is likely to be
only a partial list as not all journals are covered by
either method. However, we are continually building up the citation data
so more and more references will be included with time.
Where a reference describes a PDB structure, the PDB
codes are
shown on the right.
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Links
