Crystal Structure of α-1,4-Glucan Lyase, a Unique Glycoside Hydrolase Family Member with a Novel Catalytic Mechanism

Rozeboom, H.J.; Yu, Shukun; Madrid, Susan; Kalk, Kor H.; Zhang, Ran; Dijkstra, Bauke W.

doi:10.1074/jbc.m113.485896

Cited by 23 publications

(33 citation statements)

References 48 publications

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“…20 The crystal structure and the active pocket are shown in Fig. 20 The crystal structure and the active pocket are shown in Fig.…”

Section: Computational Modelmentioning

confidence: 99%

“…Since no water molecule takes part in the reaction and the product 1,5-anhydrofructose is clearly different from those of other glycosidases, GLases form the subgroup 2 of GH31. [17][18][19][20] The formation of the covalent glycosyl-enzyme intermediate has been observed by trapping with 5-uoro-b-L-idopyranosyl uoride, and subsequent detection and sequencing of the labeled peptide by mass spectrometry. Previous experimental studies by kinetic isotope effects have suggested that the GLasescatalyzed reaction follows a two-step mechanism which involves both the glycosylation and deglycosylation steps.…”

Section: Introductionmentioning

confidence: 99%

“…20 Based on the analyses of active site structures, they further proposed that the catalytic nucleophile (D553) which forms the covalent enzyme-glycosyl intermediate in the glycosylation step also acts as the catalytic base in the elimination step. 20 Based on the analyses of active site structures, they further proposed that the catalytic nucleophile (D553) which forms the covalent enzyme-glycosyl intermediate in the glycosylation step also acts as the catalytic base in the elimination step.…”

Section: Introductionmentioning

confidence: 99%

“…[17][18][19] But if the substrate 5-uoro-a-D-glucosyl uoride was used, the deglycosylation step was suggested to be rate-limiting. 20 Since D553 plays a dual role in the catalytic cycle and no other residue is available to abstract the C-2 proton, and the C-2 proton should be acidied by the largely broken of C-O bond allowing its facile removal, the E1-like E2 concerted mechanism should be reconsidered. 18 But a base responsible for the H-2 abstraction is required, which was not clear at that time.…”

Section: Introductionmentioning

confidence: 99%

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A QM/MM study of the catalytic mechanism of α-1,4-glucan lyase from the red seaweed Gracilariopsis lemaneiformis

Dong

Liu

2014

RSC Adv.

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a-1,4-Glucan lyase (GLase, EC 4.2.2.13), a unique glycoside hydrolase family member, specifically cleaves the a-1,4-glucosidic linkages in glycogen, starch and malto-oligosaccharides to produce 1,5-anhydro-Dfructose from the non-reducing end. Previous studies have proved that GLase belongs to the retaining glycoside lyase, and the catalytic reaction contains both the glycosylation and deglycosylation/ elimination steps, in which a covalent glycosyl-enzyme intermediate is involved. On the basis of the newly reported crystal structure of GLase (2X2I) and the speculated mechanism, the whole catalytic cycle of GLase has been studied by using a QM/MM method. Calculation results indicate that the whole catalytic cycle contains five elementary steps. Firstly, the aspartic acid residue D665 acts as an acid to protonate the glycoside oxygen, which is concerted with the cleavage of the glycoside bond. Then, the residue D553 functions as the nucleophile to attack the anomeric carbon to form the glycosyl-enzyme intermediate. Different from the retaining a-glucosidases whose glycosylation is a typical concerted process, the glycosylation process of glycosidic lyase follows a stepwise mechanism. For the deglycosylation/elimination step, two cases with or without the maltotriose group in the active site were considered. The departure of the maltotriose can facilitate the proceeding of this process. The deprotonated aspartic acid residue D553 further acts as a catalytic base to abstract the C2-proton of the glucosyl residue. The proton abstraction in the deglycosylation/elimination step is calculated to be the rate-limiting step of the whole catalytic reaction, which corresponds to the energy barriers of 20.69 and 18.53 kcal mol À1 for both of the two cases.Scheme 1 Catalytic reaction of glucan lyase.Scheme 2 Comparison of the catalytic mechanisms of alpha-1,4-glucan lyase (A and B) and alpha-glycosidase (A and B 0 ). This journal is

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“…20 The crystal structure and the active pocket are shown in Fig. 20 The crystal structure and the active pocket are shown in Fig.…”

Section: Computational Modelmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 2 more Smart Citations

A QM/MM study of the catalytic mechanism of α-1,4-glucan lyase from the red seaweed Gracilariopsis lemaneiformis

Dong

Liu

2014

RSC Adv.

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“…Hence, the H-2 is acidified during bond cleavage via the formation of cation character at C-1 and may then be abstracted by the catalytic base. Structural data show the catalytic nucleophile positioned over H-2 in structures of the covalent intermediate, implying that the role of the catalytic base is fulfilled by the nucleophile itself (Rozeboom et al, 2013).…”

Section: A-glucan Lyasesmentioning

confidence: 99%

Glycosidases: Functions, Families and Folds

Kötzler

Hancock

Withers

2014

Encyclopedia of Life Sciences

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Based in part on the previous version of this eLS article ' Glycosidases: Functions, Families and Folds' (2007) by Susan M Hancock and Stephen G Withers.Glycosidases catalyse the hydrolysis of glycosidic linkages, thereby degrading oligosaccharides and glycoconjugates, the structurally most diverse class of biopolymers. These efficient and highly specific catalysts play important roles in biological processes thus a detailed knowledge of glycosidase function is invaluable for understanding and controlling diseases and for industrial applications. The classification of this huge class of enzymes into families on the basis of amino acid sequence has provided a highly valuable tool for the analysis of structure-function relationships. Furthermore, the steady increase in three-dimensional structural information is revealing further evolutionary relationships between glycosidase families. In addition to the majority of glycosidases that act via the classical Koshland mechanisms, a growing number of such enzymes that use unusual mechanisms are being uncovered. This confluence of bioinformatics, structural and mechanistic studies has greatly advanced glycosidase engineering and the development of specific glycosidase inhibitors.

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Crystal structure of the Enterococcus faecalis α‐N‐acetylgalactosaminidase, a member of the glycoside hydrolase family 31

Miyazaki

Park

2020

FEBS Letters

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Crystal Structure of α-1,4-Glucan Lyase, a Unique Glycoside Hydrolase Family Member with a Novel Catalytic Mechanism

Cited by 23 publications

References 48 publications

A QM/MM study of the catalytic mechanism of α-1,4-glucan lyase from the red seaweed Gracilariopsis lemaneiformis

A QM/MM study of the catalytic mechanism of α-1,4-glucan lyase from the red seaweed Gracilariopsis lemaneiformis

Glycosidases: Functions, Families and Folds

Crystal structure of the Enterococcus faecalis α‐N‐acetylgalactosaminidase, a member of the glycoside hydrolase family 31

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