Mixed-Linkage Cellooligosaccharides: A New Class of Glycoside Hydrolase Inhibitors

Fort, Sébastien; Varrot, A.; Schülein, M.; Cottaz, Sylvain; Driguez, Hugues; Davies, G.J.

doi:10.1002/1439-7633(20010504)2:5<319::aid-cbic319>3.0.co;2-q

Cited by 21 publications

(12 citation statements)

References 51 publications

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“…This is in contrast to several well-characterized exo-and endoacting ␤-D-glycoside hydrolases in which the subsite Ϫ1 glycosyl residues are distorted significantly (Sulzenbacher et al, 1996;Tews et al, 1996Tews et al, , 1997Davies et al, 1998;Zou et al, 1999;Fort et al, 2001;Papanikolau et al, 2001). …”

Section: Discussioncontrasting

confidence: 80%

“…This value is ‫5.2ف‬ times lower than the inhibition found with G4SG4OG4SG4OG4SG (K i ϭ 614.6 M) ) and parallels the findings on hydrolytic preferences (Table 1). The K i values of thiooligosaccharide inhibitors for ␤-D-glycosidase hydrolases vary within the micromolar (Sulzenbacher et al, 1996;Czjzek et al, 2001;Fort et al, 2001;) ( Figure 3B) and millimolar (Moreau et al, 1996;ReverbelLeroy et al, 1998) ranges.…”

Section: Inhibition Kineticsmentioning

confidence: 85%

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Structural Basis for Broad Substrate Specificity in Higher Plant β-d-Glucan Glucohydrolases

et al. 2002

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Family 3 ␤ -D -glucan glucohydrolases are distributed widely in higher plants. The enzymes catalyze the hydrolytic removal of ␤ -D -glucosyl residues from nonreducing termini of a range of ␤ -D -glucans and ␤ -D -oligoglucosides. Their broad specificity can be explained by x-ray crystallographic data obtained from a barley ␤ -D -glucan glucohydrolase in complex with nonhydrolyzable S -glycoside substrate analogs and by molecular modeling of enzyme/substrate complexes. The glucosyl residue that occupies binding subsite ؊ 1 is locked tightly into a fixed position through extensive hydrogen bonding with six amino acid residues near the bottom of an active site pocket. In contrast, the glucosyl residue at subsite ؉ 1 is located between two Trp residues at the entrance of the pocket, where it is constrained less tightly. The relative flexibility of binding at subsite ؉ 1, coupled with the projection of the remainder of bound substrate away from the enzyme's surface, means that the overall active site can accommodate a range of substrates with variable spatial dispositions of adjacent ␤ -D -glucosyl residues. The broad specificity for glycosidic linkage type enables the enzyme to perform diverse functions during plant development. INTRODUCTION␤ -D -Glucan glucohydrolases have been purified and characterized from barley seedlings, maize coleoptiles, soybean cultures, Acacia cells, nasturtium cells, and cultured tobacco cells (Cline and Albersheim, 1981;Nari et al., 1982;Lienart et al., 1986;Labrador and Nevins, 1989;Hrmova et al., 1996;Kotake et al., 1997;Crombie et al., 1998;Kim et al., 2000;Koizumi et al., 2000). They can hydrolyze glycosidic linkages in several ␤ -D -glucans, in ␤ -D -oligoglucosides containing (1 → 2)-, (1 → 3)-, (1 → 4)-, or (1 → 6)-linkages, in aryl ␤ -D -glucosides such as 4 Ј -nitrophenyl ␤ -D -glucopyranoside (4NPGlc), and in some ␤ -D -oligoxyloglucosides (Crombie et al., 1998;Hrmova and Fincher, 1998;Kim et al., 2000). The barley ␤ -D -glucan glucohydrolases also hydrolyze cyanogenic ␤ -D -glucosides, albeit with low activity (M. Hrmova and G.B. Fincher, unpublished data). Single Glc molecules are released from the nonreducing termini of these substrates, with retention of the anomeric configuration (Hrmova et al., 1996). Their broad substrate specificity makes it difficult to assign these higher plant ␤ -D -glucan glucohydrolases to current Enzyme Commission classes; therefore, they have been described variously as ␤ -D -glucan glucohydrolases, (1 → 3)-␤ -D -glucan exohydrolases, and ␤ -D -glucosidases. Nevertheless, they can be classified according to the structural criteria of Henrissat (1991) and fall into the family 3 group of glycoside hydrolases (http://afmb.cnrsmrs.fr/CAZY/).The distribution of the broad-specificity ␤ -D -glucan glucohydrolases in various tissues of monocotyledons and dicotyledons, together with the presence of expressed sequence tags in gymnosperm sequence databases (e.g., Pinus taeda ), suggests that they may play a fundamental role in plant growth and development...

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Section: Discussioncontrasting

confidence: 80%

Section: Inhibition Kineticsmentioning

confidence: 85%

Structural Basis for Broad Substrate Specificity in Higher Plant β-d-Glucan Glucohydrolases

et al. 2002

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“…Our observation is similar to those made with B. agaradherans Cel5A. 32 In that case, upon incubation with a mainly all b-1,4-linked tetrasaccharide a trace of mixed a/b contaminant, with a single a-1,4-glycosidic linkage, was found preferentially bound in the crystal. We are attempting to confirm the formation and binding of our mixedlink b-1,3-1,4-ligand in solution.…”

Section: Discussionsupporting

confidence: 89%

Crystal Complex Structures Reveal How Substrate is Bound in the −4 to the +2 Binding Sites of Humicola grisea Cel12A

Sandgren

Berglund

Shaw³

et al. 2004

Journal of Molecular Biology

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“…Thioglycosides have been synthesized by glycosylation of thioacceptors with activated glycosyl donors,10–12 by the S N 2 reaction of 1‐thio sugars with activated acceptors,13 and by Michael‐like addition of 1‐thiosugars to α,β‐unsaturated systems;14 all routes involve numerous protection and deprotection steps and require good control of anomeric stereochemistry.…”

Section: Methodsmentioning

confidence: 99%

Thioglycoligases: Mutant Glycosidases for Thioglycoside Synthesis

et al. 2003

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Mixed-Linkage Cellooligosaccharides: A New Class of Glycoside Hydrolase Inhibitors

Cited by 21 publications

References 51 publications

Structural Basis for Broad Substrate Specificity in Higher Plant β-d-Glucan Glucohydrolases

Structural Basis for Broad Substrate Specificity in Higher Plant β-d-Glucan Glucohydrolases

Crystal Complex Structures Reveal How Substrate is Bound in the −4 to the +2 Binding Sites of Humicola grisea Cel12A

Thioglycoligases: Mutant Glycosidases for Thioglycoside Synthesis

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