Structural and Mechanistic Classification of Uronic Acid-Containing Polysaccharide Lyases Garron, Marie-Line; Cygler, Miroslaw

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Structural and Mechanistic Classification of Uronic Acid-Containing Polysaccharide Lyases Garron, Marie-Line; Cygler, Miroslaw NRC Publications Archive Archives des publications du CNRC Structural and mechanistic classification of uronic acid-containing polysaccharide lyases Garron, Marie-Line; Cygler, Miroslaw This publication could be one of several versions: author’s original, accepted manuscript or the publisher’s version. / La version de cette publication peut être l’une des suivantes : la version prépublication de l’auteur, la version acceptée du manuscrit ou la version de l’éditeur. For the publisher’s version, please access the DOI link below./ Pour consulter la version de l’éditeur, utilisez le lien DOI ci-dessous. Publisher’s version / Version de l'éditeur: https://doi.org/10.1093/glycob/cwq122 Glycobiology, 20, 12, pp. 1547-1573, 2010-08-30 NRC Publications Record / Notice d'Archives des publications de CNRC: https://nrc-publications.canada.ca/eng/view/object/?id=8899cf95-74fa-40ce-8f57-15085cad602e https://publications-cnrc.canada.ca/fra/voir/objet/?id=8899cf95-74fa-40ce-8f57-15085cad602e Access and use of this website and the material on it are subject to the Terms and Conditions set forth at https://nrc-publications.canada.ca/eng/copyright READ THESE TERMS AND CONDITIONS CAREFULLY BEFORE USING THIS WEBSITE. L’accès à ce site Web et l’utilisation de son contenu sont assujettis aux conditions présentées dans le site https://publications-cnrc.canada.ca/fra/droits LISEZ CES CONDITIONS ATTENTIVEMENT AVANT D’UTILISER CE SITE WEB. Questions? Contact the NRC Publications Archive team at [email protected]. If you wish to email the authors directly, please see the first page of the publication for their contact information. Vous avez des questions? Nous pouvons vous aider. Pour communiquer directement avec un auteur, consultez la première page de la revue dans laquelle son article a été publié afin de trouver ses coordonnées. Si vous n’arrivez pas à les repérer, communiquez avec nous à [email protected]. Glycobiology vol. 20 no. 12 pp. 1547–1573, 2010 doi:10.1093/glycob/cwq122 Advance Access publication on August 30, 2010 REVIEW Structural and mechanistic classification of uronic acid-containing polysaccharide lyases Marie-Line Garron2, and Miroslaw Cygler1,2,3 are involved in various cellular processes, including signal 2 transmission (Mythreye and Blobe 2009; Schaefer and Schaefer Department of Biochemistry, McGill University, 3655 Promenade Sir William Downloaded from Osler, Montreal, Quebec, Canada H3G 1Y6; and 3Biotechnology Research 2010), immune response (Chen et al. 2008; Marth and Grewal Institute, NRC, 6100 Royalmount Avenue, Montreal, Quebec, Canada 2008), bacterial pathogenesis (Boneca 2005), and cancer H4P 2R2 progression (Vlodavsky et al. 2007; Iozzo et al. 2009). Polysac- Received on June 1, 2010; revised on August 6, 2010; accepted on charides are most frequently found on cell surfaces in uni- and August 11, 2010 multicellular organisms (Gabius 2006) and in the extracellular matrix of higher eukaryotes (Iozzo 1998) and are essential com- glycob.oxfordjournals.org Polysaccharide lyases (PLs) have been assigned to 21 fam- ponents of cell wall of plants (Knox 2008; Sarkar et al. 2009). ilies based on their sequences, with ~50 singletons awaiting Within the extracellular matrix, they fulfill architectural func- further classification. For 19 of these families, the structure tions providing elasticity (Knudson and Knudson 2001; Scott of at least one protein is known. In this review, we have 2003) and serve as storage for many growth factors and other analyzed the available structural information and show proteins (Macri et al. 2007). They form the building blocks of that presently known PL families belong to six general cell walls, providing physical rigidity and protection against folds. Only two general catalyticmechanismshavebeen the environment. Oligosaccharides are utilized for signaling dur- observed among these PLs: (1) metal-assisted neutraliza- ing protein folding (Parodi 2000) and decorate many secreted tion of the acidic group of the sugar next to the cleaved proteins (Ohtsubo and Marth 2006). Many of these biologically at Canada Institute for STI on March 30, 2011 bond, with, rather unusually, arginine or lysine playing important polysaccharides contain uronic acid within their the role of Brønsted base and (2) neutralization of the acidic repeating units. group on the sugar by a close approach of an amino or acidic Not surprisingly, all organisms contain a large number of en- group forcing its protonation and Tyr or Tyr-His acting as zymes dedicated to polysaccharide synthesis, modification, and the Brønsted base and acid. degradation (Lairson et al. 2008). Some bacteria and plants re- lay on polysaccharides as a carbon source and contain an Keywords: polysaccharide lyases/glycosaminoglycans/ unusually large contingent of such enzymes (e.g. commensal classification/enzymatic mechanism/fold analysis Bacteroides thetaiotaomicron). The up-to-date classification of enzymes that degrade, modify, or create glycosidic bonds is maintained in the Carbohydrate Active enZYmes (CAZy) database (http://www.cazy.org/) (Cantarel et al. 2009). Carbo- Introduction hydrate modifying enzymes are divided into four classes: glycoside hydrolases (GHs), glycosyltransferases (GTs), poly- Carbohydrates are a large class of essential molecules common saccharide lyases (PLs), and carbohydrate esterases (CEs). The to all organisms. They are found most abundantly as polymers, structure and mechanisms of GHs and GTs have been exten- either as oligo- or polysaccharides, usually linked to proteins or sively studied and frequently reviewed, most recently in lipids. Carbohydrates possess a multiplicity of chiral centers (Henrissat et al. 2008). On the other hand, only limited reviews fi fi and a large number of speci c modi cations, including acety- of specific families of PLs have been published (Jenkins et al. lation, methylation, oxidation, and sulfonation, creating great 1998; Hashimoto et al. 2005; Linhardt et al. 2006). The pur- chemical diversity from simple carbohydrate building blocks pose of this review is to analyze and compare the structural (Gabius 2000; Bertozzi and Kiessling 2001; Cummings and and mechanistic features of PLs and to classify them based Stephen 2007). Polysaccharides are polymers formed of carbo- on their fold and catalytic mechanism. hydrate repeating units joined by glycosidic bonds. These are Two chemical reactions are predominantly utilized for enzy- predominantly linear polymers but may contain various degrees matic depolymerization of polysaccharide chains: hydrolysis of branching. Polysaccharides are essential cellular components and lytic β-elimination (Yip and Withers 2004). Hydrolysis of all living organisms and play multiple biological roles proceeds through the addition of a water molecule to break (Gagneux and Varki 1999; Schaefer and Schaefer 2010). They the glycosidic bond, creating a new reducing end on one frag- ment, with either retention or inversion of the configuration at 1To whom correspondence should be addressed: Tel: +1-514-496-6321; C-1, and a saturated hexose ring on the nonreducing end of the Fax: +1-514-496-5143; e-mail: [email protected] other fragment (McCarter and Withers 1994). β-Eliminative © The Author 2010. Published by Oxford University Press. All rights reserved. For permissions, please e-mail: [email protected] 1547 M-L Garron and M Cygler cleavage of a glycosidic bond can occur when the sugar is sub- enzymes, the subsites −2 to +2 are the most important determi- stituted with an acidic group next to the carbon forming the nants of substrate specificity. glycosidic bond and results in the formation of a reducing In this review, we analyze the available data on the structure end on one fragment and an unsaturated ring on the nonre- and catalytic mechanisms of PLs and group the PL families ducing end of the second fragment. The chemical steps of into classes based on their folds. this mechanism were proposed by Gacesa (1987).Glucanpoly- saccharides can also be degraded by phosphorolysis by such enzymes as α-glucan phosphorylases (Withers et al. 1981). Substrates of PLs Eukaryotic enzymes that depolymerize polysaccharides PL substrates have different origins: bacterial, plant, or animal. predominantly utilize hydrolytic mechanisms while the lytic Nevertheless, they present relatively similar chemical struc- mechanism is found in many enzymes of bacterial or fungal or- tures composed of repetitive blocks of pyranoses. Each block igin as well as in plants and algae. In this review, we will discuss is composed of two to five saccharides linked by a (1-4) gly- only PLs. cosidic bond. PLs described here require an acidic group at +1 PLs act on polysaccharides containing a hexose oxidized at sugar. Based on the nature of the +1 sugar, the substrates of PLs C-5 position to a carboxylic group and use β-elimination can be divided into three groups: (1) galacturonic acid, (2) Downloaded from mechanism to cleave the glycosidic bond at the C-4 position. glucuronic/iduronic acid, and (3) mannuronate/guluronate. Three chemical steps have been proposed to occur during the Polysaccharides in the first group include pectate and pectin, β-elimination reaction (Figure 1A) (Gacesa 1987). First, the the second group includes hyaluronan, chondroitin, chondroitin carboxyl group of the substrate is neutralized, often by a nearby sulfate (CS), dermatan sulfate (DS), heparin, HS, heparosan, positive charge, to reduce the pKa of
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