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Active site of chondroitin AC lyase revealed by the structure of enzyme-oligosaccharide complexes and mutagenesis.

Huang W, Boju L, Tkalec L, Su H, Yang HO, Gunay NS, Linhardt RJ, Kim YS, Matte A, Cygler M
Biochemistry 40 2359-72 (2001)
Related entries: 1hm2, 1hmu, 1hmw

Cited: 47 times
EuropePMC logo PMID: 11327856

Abstract

The crystal structures of Flavobacterium heparinium chondroitin AC lyase (chondroitinase AC; EC 4.2.2.5) bound to dermatan sulfate hexasaccharide (DS(hexa)), tetrasaccharide (DS(tetra)), and hyaluronic acid tetrasaccharide (HA(tetra)) have been refined at 2.0, 2.0, and 2.1 A resolution, respectively. The structure of the Tyr234Phe mutant of AC lyase bound to a chondroitin sulfate tetrasaccharide (CS(tetra)) has also been determined to 2.3 A resolution. For each of these complexes, four (DS(hexa) and CS(tetra)) or two (DS(tetra) and HA(tetra)) ordered sugars are visible in electron density maps. The lyase AC DS(hexa) and CS(tetra) complexes reveal binding at four subsites, -2, -1, +1, and +2, within a narrow and shallow protein channel. We suggest that subsites -2 and -1 together represent the substrate recognition area, +1 is the catalytic subsite and +1 and +2 together represent the product release area. The putative catalytic site is located between the substrate recognition area and the product release area, carrying out catalysis at the +1 subsite. Four residues near the catalytic site, His225, Tyr234, Arg288, and Glu371 together form a catalytic tetrad. The mutations His225Ala, Tyr234Phe, Arg288Ala, and Arg292Ala, revealed residual activity for only the Arg292Ala mutant. Structural data indicate that Arg292 is primarily involved in recognition of the N-acetyl and sulfate moieties of galactosamine, but does not participate directly in catalysis. Candidates for the general base, removing the proton attached to C-5 of the glucuronic acid at the +1 subsite, are Tyr234, which could be transiently deprotonated during catalysis, or His225. Tyrosine 234 is a candidate to protonate the leaving group. Arginine 288 likely contributes to charge neutralization and stabilization of the enolate anion intermediate during catalysis.

Reviews - 1hm3 mentioned but not cited (1)

  1. Atomic-Resolution Experimental Structural Biology and Molecular Dynamics Simulations of Hyaluronan and Its Complexes. Guvench O. Molecules 27 7276 (2022)

Articles - 1hm3 mentioned but not cited (1)

  1. GlycoPP: a webserver for prediction of N- and O-glycosites in prokaryotic protein sequences. Chauhan JS, Bhat AH, Raghava GP, Rao A. PLoS One 7 e40155 (2012)


Reviews citing this publication (9)

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Articles citing this publication (36)

  1. High-resolution crystal structure of Arthrobacter aurescens chondroitin AC lyase: an enzyme-substrate complex defines the catalytic mechanism. Lunin VV, Li Y, Linhardt RJ, Miyazono H, Kyogashima M, Kaneko T, Bell AW, Cygler M. J Mol Biol 337 367-386 (2004)
  2. The structure of chondroitin B lyase complexed with glycosaminoglycan oligosaccharides unravels a calcium-dependent catalytic machinery. Michel G, Pojasek K, Li Y, Sulea T, Linhardt RJ, Raman R, Prabhakar V, Sasisekharan R, Cygler M. J Biol Chem 279 32882-32896 (2004)
  3. Chondroitinase ABC I from Proteus vulgaris: cloning, recombinant expression and active site identification. Prabhakar V, Capila I, Bosques CJ, Pojasek K, Sasisekharan R. Biochem J 386 103-112 (2005)
  4. Crystal structure of Proteus vulgaris chondroitin sulfate ABC lyase I at 1.9A resolution. Huang W, Lunin VV, Li Y, Suzuki S, Sugiura N, Miyazono H, Cygler M. J Mol Biol 328 623-634 (2003)
  5. Convergent evolution sheds light on the anti-beta -elimination mechanism common to family 1 and 10 polysaccharide lyases. Charnock SJ, Brown IE, Turkenburg JP, Black GW, Davies GJ. Proc Natl Acad Sci U S A 99 12067-12072 (2002)
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  7. Biochemical characterization of the chondroitinase ABC I active site. Prabhakar V, Raman R, Capila I, Bosques CJ, Pojasek K, Sasisekharan R. Biochem J 390 395-405 (2005)
  8. The K5 lyase KflA combines a viral tail spike structure with a bacterial polysaccharide lyase mechanism. Thompson JE, Pourhossein M, Waterhouse A, Hudson T, Goldrick M, Derrick JP, Roberts IS. J Biol Chem 285 23963-23969 (2010)
  9. Catalytic mechanism of heparinase II investigated by site-directed mutagenesis and the crystal structure with its substrate. Shaya D, Zhao W, Garron ML, Xiao Z, Cui Q, Zhang Z, Sulea T, Linhardt RJ, Cygler M. J Biol Chem 285 20051-20061 (2010)
  10. Origin and diversity of alginate lyases of families PL-5 and -7 in Sphingomonas sp. strain A1. Miyake O, Ochiai A, Hashimoto W, Murata K. J Bacteriol 186 2891-2896 (2004)
  11. Structures of Streptococcus pneumoniae hyaluronate lyase in complex with chondroitin and chondroitin sulfate disaccharides. Insights into specificity and mechanism of action. Rigden DJ, Jedrzejas MJ. J Biol Chem 278 50596-50606 (2003)
  12. The structural bases of the processive degradation of iota-carrageenan, a main cell wall polysaccharide of red algae. Michel G, Helbert W, Kahn R, Dideberg O, Kloareg B. J Mol Biol 334 421-433 (2003)
  13. Crystal structure of Bacillus sp. GL1 xanthan lyase, which acts on the side chains of xanthan. Hashimoto W, Nankai H, Mikami B, Murata K. J Biol Chem 278 7663-7673 (2003)
  14. Crystal structure of unsaturated glucuronyl hydrolase, responsible for the degradation of glycosaminoglycan, from Bacillus sp. GL1 at 1.8 A resolution. Itoh T, Akao S, Hashimoto W, Mikami B, Murata K. J Biol Chem 279 31804-31812 (2004)
  15. Recombinant expression, purification, and biochemical characterization of chondroitinase ABC II from Proteus vulgaris. Prabhakar V, Capila I, Soundararajan V, Raman R, Sasisekharan R. J Biol Chem 284 974-982 (2009)
  16. Structural and mutational characterization of the catalytic A-module of the mannuronan C-5-epimerase AlgE4 from Azotobacter vinelandii. Rozeboom HJ, Bjerkan TM, Kalk KH, Ertesvåg H, Holtan S, Aachmann FL, Valla S, Dijkstra BW. J Biol Chem 283 23819-23828 (2008)
  17. Composite active site of chondroitin lyase ABC accepting both epimers of uronic acid. Shaya D, Hahn BS, Bjerkan TM, Kim WS, Park NY, Sim JS, Kim YS, Cygler M. Glycobiology 18 270-277 (2008)
  18. Structural insights into marine carbohydrate degradation by family GH16 κ-carrageenases. Matard-Mann M, Bernard T, Leroux C, Barbeyron T, Larocque R, Préchoux A, Jeudy A, Jam M, Nyvall Collén P, Michel G, Czjzek M. J Biol Chem 292 19919-19934 (2017)
  19. Induced-fit motion of a lid loop involved in catalysis in alginate lyase A1-III. Mikami B, Ban M, Suzuki S, Yoon HJ, Miyake O, Yamasaki M, Ogura K, Maruyama Y, Hashimoto W, Murata K. Acta Crystallogr D Biol Crystallogr 68 1207-1216 (2012)
  20. Crystal structure of Bacillus sp. GL1 xanthan lyase complexed with a substrate: insights into the enzyme reaction mechanism. Maruyama Y, Hashimoto W, Mikami B, Murata K. J Mol Biol 350 974-986 (2005)
  21. A polysaccharide lyase from Stenotrophomonas maltophilia with a unique, pH-regulated substrate specificity. MacDonald LC, Berger BW. J Biol Chem 289 312-325 (2014)
  22. Gene cloning and functional analysis of glycosaminoglycan-degrading enzyme chondroitin AC lyase from Flavobacterium columnare G4. Xie HX, Nie P, Chang MX, Liu Y, Yao WJ. Arch Microbiol 184 49-55 (2005)
  23. Uncovering the Catalytic Direction of Chondroitin AC Exolyase: FROM THE REDUCING END TOWARDS THE NON-REDUCING END. Yin FX, Wang FS, Sheng JZ. J Biol Chem 291 4399-4406 (2016)
  24. Biochemical characterization of a novel ulvan lyase from Pseudoalteromonas sp. strain PLSV. Qin HM, Xu P, Guo Q, Cheng X, Gao D, Sun D, Zhu Z, Lu F. RSC Adv 8 2610-2615 (2018)
  25. The crystal structure of novel chondroitin lyase ODV-E66, a baculovirus envelope protein. Kawaguchi Y, Sugiura N, Kimata K, Kimura M, Kakuta Y. FEBS Lett 587 3943-3948 (2013)
  26. An evolutionarily distinct family of polysaccharide lyases removes rhamnose capping of complex arabinogalactan proteins. Munoz-Munoz J, Cartmell A, Terrapon N, Baslé A, Henrissat B, Gilbert HJ. J Biol Chem 292 13271-13283 (2017)
  27. The crystal structure of a hyperthermoactive exopolygalacturonase from Thermotoga maritima reveals a unique tetramer. Pijning T, van Pouderoyen G, Kluskens L, van der Oost J, Dijkstra BW. FEBS Lett 583 3665-3670 (2009)
  28. The synthesis of a novel thio-linked disaccharide of chondroitin as a potential inhibitor of polysaccharide lyases. Rye CS, Withers SG. Carbohydr Res 339 699-703 (2004)
  29. An atypical approach identifies TYR234 as the key base catalyst in chondroitin AC lyase. Rye CS, Matte A, Cygler M, Withers SG. Chembiochem 7 631-637 (2006)
  30. Preparation of the methyl ester of hyaluronan and its enzymatic degradation. Hirano K, Sakai S, Ishikawa T, Avci FY, Linhardt RJ, Toida T. Carbohydr Res 340 2297-2304 (2005)
  31. A chondroitin sulfate and hyaluronic acid lyase with poor activity to glucuronyl 4,6-O-disulfated N-acetylgalactosamine (E-type)-containing structures. Peng C, Wang Q, Wang S, Wang W, Jiao R, Han W, Li F. J Biol Chem 293 4230-4243 (2018)
  32. Super-channel in bacteria: structural and functional aspects of a novel biosystem for the import and depolymerization of macromolecules. Hashimoto W, Yamasaki M, Itoh T, Momma K, Mikami B, Murata K. J Biosci Bioeng 98 399-413 (2004)
  33. Chondroitin O-methyl ester: an unusual substrate for chondroitin AC lyase. Avci FY, Toida T, Linhardt RJ. Carbohydr Res 338 2101-2104 (2003)
  34. Cloning and Characterization of a Chondroitin AC Exolyase from Arthrobacter sp. SD-04. Chen LZ, Shi CQ, Yin FX, Wang FS, Sheng JZ. Mol Biotechnol 61 791-800 (2019)
  35. Molecular docking analysis of a dermatan sulfate tetra-saccharide to human alpha-L-iduronidase. Durán-Gutiérrez DP, López-Hidalgo M, Peña-Gomar IM, Zamorano-Carrillo A, Gómez-Esquivel ML, Castrejón-Flores JL, Reyes-López CA. Bioinformation 19 1116-1123 (2023)
  36. N∆89 and C∆274 Truncated Enzymes of Chondroitinase ABC I Regain More Imperturbable Microenvironments Around Structural Components in Comparison to their Wild Type. Omidi-Ardali H, Aminian M, Golestani A, Shahaboddin ME, Maleki M. Protein J 38 151-159 (2019)


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