Recent structural insights into the expanding world of carbohydrate-active enzymes

Davies, G.J.; Gloster, T.M.; Henrissat, Bernard

doi:10.1016/j.sbi.2005.10.008

Cited by 263 publications

(198 citation statements)

References 58 publications

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“…The binuclear Mg 2ϩ center found in the active site ( Fig. 2) is a unique feature among the family of glycohydrolases (31). The ARH fold is completely different from that of arginase (PDB ID code 1RLA) (32), which contains a binuclear Mn center and which has been used in a previous study as a model for DRAG (18).…”

Section: Discussionmentioning

confidence: 99%

The structure of human ADP-ribosylhydrolase 3 (ARH3) provides insights into the reversibility of protein ADP-ribosylation

Mueller-Dieckmann

Kernstock²,

Lisurek

et al. 2006

Proc. Natl. Acad. Sci. U.S.A.

100

136

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Posttranslational modifications are used by cells from all kingdoms of life to control enzymatic activity and to regulate protein function. For many cellular processes, including DNA repair, spindle function, and apoptosis, reversible mono-and polyADP-ribosylation constitutes a very important regulatory mechanism. Moreover, many pathogenic bacteria secrete toxins which ADP-ribosylate human proteins, causing diseases such as whooping cough, cholera, and diphtheria. Whereas the 3D structures of numerous ADP-ribosylating toxins and related mammalian enzymes have been elucidated, virtually nothing is known about the structure of protein de-ADP-ribosylating enzymes. Here, we report the 3D structure of human ADP-ribosylhydrolase 3 (hARH3). The molecular architecture of hARH3 constitutes the archetype of an all-␣-helical protein fold and provides insights into the reversibility of protein ADP-ribosylation. Two magnesium ions flanked by highly conserved amino acids pinpoint the active-site crevice. Recombinant hARH3 binds free ADP-ribose with micromolar affinity and efficiently de-ADP-ribosylates poly-but not monoADP-ribosylated proteins. Docking experiments indicate a possible binding mode for ADP-ribose polymers and suggest a reaction mechanism. Our results underscore the importance of endogenous ADP-ribosylation cycles and provide a basis for structure-based design of ADP-ribosylhydrolase inhibitors.protein structure ͉ posttranslational modification ͉ glycohydrolase ͉ docking P osttranslational modifications (PTMs) are covalent modifications of amino acid side chains in proteins that come in many different sizes and shapes, ranging from the simple addition of a phosphate group to complex multistep glycosylations. Enzyme-catalyzed PTMs allow rapid responses to environmental stimuli and play crucial roles in signal transduction. NAD-dependent ADP-ribosylation is a reversible PTM in which mono-and polyADP-ribosyltransferases (ARTs and PARPs) and ADP-ribosylhydrolases (ARHs) and poly(ADP-ribose) glycohydrolases (PARGs) catalyze amino acid-specific ADPribosylation and de-ADP-ribosylation, respectively ( Fig. 1) (1-10). ADP-ribosylation has attracted attention because bacterial virulence factors, including diphtheria, cholera, and pertussis toxin, use it as part of their pathogenic mechanism (2, 11). Mono-and polyADP-ribosylation have been recognized also as regulatory mechanisms in many cellular processes, including DNA-repair, chromatin decondensation, transcription, telomere function, mitotic spindle formation, and apoptosis (5-10, 12).Several enzymes have been cloned that catalyze de-ADPribosylation of mono-or polyADP-ribosylated proteins (13-15). Dinitrogenase-activating glycohydrolase (DRAG), an Arg-specific ARH from the phototrophic bacterium Rhodospirillum rubrum, regulates a key enzyme of nitrogen fixation (16-18). The human genome encodes three DRAG-related proteins designated ARH1, ARH2, and ARH3 (19), which are 357, 354, and 363 residues long, respectively. ARH1, like DRAG, specifically de-ADP-ribosylates prote...

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Section: Discussionmentioning

confidence: 99%

The structure of human ADP-ribosylhydrolase 3 (ARH3) provides insights into the reversibility of protein ADP-ribosylation

Mueller-Dieckmann

Kernstock²,

Lisurek

et al. 2006

Proc. Natl. Acad. Sci. U.S.A.

100

136

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“…For example, cellulases are located in 11 GHs, with seven of these families distributed across four different clans, while four of these GHs currently are not linked to a clan. There have been several reviews on the three-dimensional structure of the catalytic modules of glycoside hydrolases, including plant cell walldegrading enzymes Davies, 1997, 2000;Davies et al, 2005;Gilbert et al, 2008). Therefore, this Update will provide a brief overview of the structures of these enzymes and a more detailed description of recent structural information.…”

Section: Catalytic Modules Of Glycoside Hydrolasesmentioning

confidence: 99%

The Biochemistry and Structural Biology of Plant Cell Wall Deconstruction

2010

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“…This is not surprising since members of this phylum are known as efficient degraders of various macromolecules including complex polysaccharides [8]. Genomes of these bacteria contain a significant number of genes encoding carbohydrate-processing enzymes [8][9][10][11].…”

Section: Introductionmentioning

confidence: 99%

Lateral gene transfer between the Bacteroidetes and Acidobacteria: The case of α‐l‐rhamnosidases

Naumoff

Dedysh

2012

FEBS Letters

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a b s t r a c t a-L-Rhamnosidases catalyze the hydrolysis of the terminal a-L-rhamnose residues in various carbohydrates. The catalytic domains in most of these enzymes belong to the families GH78 and GH106 of glycoside hydrolases. In this study, we show that almost all genes encoding the GH78-and GH106-containing proteins from members of the poorly characterized bacterial phylum Acidobacteria originated from precursors belonging to the phylum Bacteroidetes. Members of the Acidobacteria and Bacteroidetes display similar functional capabilities and specialize on degradation of plant-derived organic matter. Several proposed lateral gene transfers between the Acidobacteria and Bacteroidetes occurred presumably during specialization of these bacteria for their environments.

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Recent structural insights into the expanding world of carbohydrate-active enzymes

Cited by 263 publications

References 58 publications

The structure of human ADP-ribosylhydrolase 3 (ARH3) provides insights into the reversibility of protein ADP-ribosylation

The structure of human ADP-ribosylhydrolase 3 (ARH3) provides insights into the reversibility of protein ADP-ribosylation

The Biochemistry and Structural Biology of Plant Cell Wall Deconstruction

Lateral gene transfer between the Bacteroidetes and Acidobacteria: The case of α‐l‐rhamnosidases

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