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PDBsum entry 1l2a
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Contents |
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* Residue conservation analysis
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References listed in PDB file
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Key reference
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Title
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The crystal structure and catalytic mechanism of cellobiohydrolase cels, The major enzymatic component of the clostridium thermocellum cellulosome.
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Authors
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B.G.Guimarães,
H.Souchon,
B.L.Lytle,
J.H.David wu,
P.M.Alzari.
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Ref.
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J Mol Biol, 2002,
320,
587-596.
[DOI no: ]
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PubMed id
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Abstract
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Cellobiohydrolase CelS plays an important role in the cellulosome, an active
cellulase system produced by the thermophilic anaerobe Clostridium thermocellum.
The structures of the catalytic domain of CelS in complex with substrate
(cellohexaose) and product (cellobiose) were determined at 2.5 and 2.4 A
resolution, respectively. The protein folds into an (alpha/alpha)(6) barrel with
a tunnel-shaped substrate-binding region. The conformation of the loops defining
the tunnel is intrinsically stable in the absence of substrate, suggesting a
model to account for the processive mode of action of family 48
cellobiohydrolases. Structural comparisons with other (alpha/alpha)(6) barrel
glycosidases indicate that CelS and endoglucanase CelA, a sequence-unrelated
family 8 glycosidase with a groove-shaped substrate-binding region, use the same
catalytic machinery to hydrolyze the glycosidic linkage, despite a low sequence
similarity and a different endo/exo mode of action. A remarkable feature of the
mechanism is the absence, from CelS, of a carboxylic group acting as the base
catalyst. The nearly identical arrangement of substrate and functionally
important residues in the two active sites strongly suggests an evolutionary
relationship between the cellobiohydrolase and endoglucanase families, which can
therefore be classified into a new clan of glycoside hydrolases.
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Figure 4.
Figure 4. Protein-carbohydrate hydrogen bonding
interactions in the CelS-cellohexaose complex. Hydrogen bonds
are indicated with broken lines; the corresponding distances are
given in Å.
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Figure 5.
Figure 5. Structural comparison of family 48
cellobiohydrolase CelS and family 8 endoglucanase CelA. (a)
Superposition of the catalytic domains of CelS (green) and CelA
(red); bound cellooligomers are shown in CPK mode. (b) Detailed
view of the substrate-binding region and the four invariant
amino acid residues found in CelS (green) and CelA (red). (c)
Amino acid residues and the water nucleophile involved in the
catalytic mechanism of CelA and (d) the equivalent view in CelS,
including the sugar ring at subsite -1 as seen in CelA (colored
in brown). All distances are given in Å.
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The above figures are
reprinted
by permission from Elsevier:
J Mol Biol
(2002,
320,
587-596)
copyright 2002.
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