Substrate Distortion by a Lichenase Highlights the Different Conformational Itineraries Harnessed by Related Glycoside Hydrolases

Abstract

Such Dir einen Weg raus: Eine Reihe von enzymatischen Schnappschüssen entlang der Reaktionskoordinate einer Lichenase (für gluco‐konfigurierte Substrate spezifisch) belegt, dass dieses Enzym einen anderen Reaktionsweg mit einer 1S3→4H3→4C1‐Wanderung beschreitet als nahe verwandte Mannanasen.

Crystal Structures of Paenibacillus polymyxa β-Glucosidase B Complexes Reveal the Molecular Basis of Substrate Specificity and Give New Insights into the Catalytic Machinery of Family I Glycosidases

“…[38][39][40][41][42][43] It was proposed recently that structurally related enzymes do not necessarily adopt the same catalytic pathways and, in general, exo-acting enzymes in which the glycone sugar is not tethered to an extended oligosaccharide chain, are able to explore larger conformational space than endo-acting enzymes whose subsite −1 glycone is necessarily restrained by the oligosaccharide chain to which it is linked. 47 Consequently, structurally related enzymes working on chemically different sugars may harness alternative agendas that reflect the chemistry of their substrate. Furthermore, trapped Michaelis complexes with axial leaving groups have been reported showing different conformations at the −1 site ring.…”

Dissecting conformational contributions to glycosidase catalysis and inhibition

“…Family GH26 contains enzymes that act on β-mannosides, β-glucosides and β-xylosides: lichenases (which hydrolyse the mixed linkage β-1,3-; β-1,4-glucan lichenan), β-mannanase and β-1,3-xylanases. Studies of Michaelis complexes and trapped glycosyl enzymes provides good evidence for an alternative 1 S 3 → 4 H 3 ‡ → 4 C 1 itinerary for lichenases [45] and β-1,3-xylanases [46 • ]. The different conformations of the transition state of the d - gluco / d - xylo and d - manno configured substrates result in the substituents at C2 being pseudo-equatorial in both cases and lying at essentially the same place in space, explaining how the conserved catalytic machinery of different GH26 family members can tolerate differently configured sugars, with the specificity arising from a large difference in the positions of the C3 substituents [45], a relationship which is highlighted by the common inhibition of β-mannosidases and β-glucosidases by isofagomine lactam [47].…”

“Amide Resonance” in the Catalysis of 1,2-α-l-Fucosidase from Bifidobacterium bifidum

“…Another important issue deserves special consideration for the hydrolysis of glycosydic bond is the conformational changes for the nonreducing sugar ring. It has been suggested that the general conformational change of the sugar ring at the nonreducing end should follow the Stoddard diagram. − As discussed by many previous works on glycosidases, in order to facilitate the hydrolysis of glycosidic bond, the conformation of the nonreducing sugar unit might take some conformational distortion from the chair shape. , To examine the conformational change during the reaction, we have employed Berces’ definition of torsion angles, in which a general data set of T = {τ 1 , τ 2 , τ 3 , τ 4 , τ 5 , τ 6 } is defined as a vector of six endocyclic torsion angles of C 1 C 2 C 3 C4, C 2 C 3 C 4 C 5 , C 3 C 4 C 5 O 5 , C 4 C 5 O 5 C 1 , C 5 O 5 C 1 C 2 , and O 5 C 1 C 2 C 3 , respectively. In Table , we listed six torsion angles for the Fuc unit.…”

“…53−55 As discussed by many previous works on glycosidases, in order to facilitate the hydrolysis of glycosidic bond, the conformation of the nonreducing sugar unit might take some conformational distortion from the chair shape. 34,54 To examine the conformational change during the reaction, we have employed Berces' definition of torsion angles, 56 in which a general data set of T = {τ 1 , τ 2 , τ 3 , τ 4 , τ 5 , τ 6 } is defined as a vector of six endocyclic torsion angles of…”