Biochemical and structural studies of a l-haloacid dehalogenase from the thermophilic archaeon Sulfolobus tokodaii

Springer Science and Business Media LLC - Tập 13 - Trang 179-190 - 2008
Carrie A. Rye1, Michail N. Isupov1, Andrey A. Lebedev2,1, Jennifer A. Littlechild1
1Henry Wellcome Building for Biocatalysis, School of Biosciences, University of Exeter, Exeter, UK
2Structural Biology Laboratory, Department of Chemistry, University of York, York, UK

Tóm tắt

Haloacid dehalogenases have potential applications in the pharmaceutical and fine chemical industry as well as in the remediation of contaminated land. The l-2-haloacid dehalogenase from the thermophilic archaeon Sulfolobus tokodaii has been cloned and over-expressed in Escherichia coli and successfully purified to homogeneity. Here we report the structure of the recombinant dehalogenase solved by molecular replacement in two different crystal forms. The enzyme is a homodimer with each monomer being composed of a core-domain of a β-sheet bundle surrounded by α-helices and an α-helical sub-domain. This fold is similar to previously solved mesophilic l-haloacid dehalogenase structures. The monoclinic crystal form contains a putative inhibitor l-lactate in the active site. The enzyme displays haloacid dehalogenase activity towards carboxylic acids with the halide attached at the C2 position with the highest activity towards chloropropionic acid. The enzyme is thermostable with maximum activity at 60°C and a half-life of over 1 h at 70°C. The enzyme is relatively stable to solvents with 25% activity lost when incubated for 1 h in 20% v/v DMSO.

Tài liệu tham khảo

Allpress JD, Gowland PC (1998) Dehalogenases: environmental defence mechanism and model of enzyme evolution. Biochem Education 26:267–276 Arai R, Kukimoto-Niino M, Kuroishi C, Bessho Y, Shirouzu M, Yokoyama S (2006) Crystal structure of the probable haloacid dehalogenase PH0459 from Pyrococcus horikoshii OT3. Protein Sci 15:373–377 CCP4. Collaborative Computational Project, Number 4 (1994) Acta Cryst D 50:760–763 Diez A, Prieto MI, Alvarez MJ, Bautista JM, Garrido J, Puyet A (1996) Improved catalytic performance of a 2-haloacid dehalogenase from Azotobacter sp. by ion-exchange immobilisation. Biochem Biophys Res Comm 220:828–833 Emsley P, Cowtan K (2004) COOT: model-building tools for molecular graphics. Acta Cryst D 60:2184–2195 Esnouf RM (1997) An extensively modified version of MOLSCRIPT that includes greatly enhanced colouring capabilities. J Mol Graph Model 15:132–134 Hisano T, Hata Y, Fujii T, Liu JQ, Kurihara T, Esaki N, Soda K (1996) Crystal structure of l-2-haloacid dehalogenase from Pseudomonas sp. YL. J Biol Chem 271:20322–20330 Kawarabayasi Y, Hino Y, Horikawa H, Jin-no K, Takahashi M, Sekine M, Baba S, Ankai A, Kosugi H, Hosoyama A, Fukui S, Nagai Y, Nishijima K, Otsuka R, Nakazawa H, Takamiya M, Kato Y, Yoshizawa T, Tanaka T, Kudoh Y, Yamazaki J, Kushida N, Oguchi A, Aoki K, Masuda S, Yanagii M, Nishimura M, Yamagishi A, Oshima T, Kikuchi H (2001) Complete genome sequence of an aerobic thermoacidophilic crenarchaeon Sulfolobus tokodaii strain 7. DNA Res 8:123–140 Kurihara T, Liu JQ, Nardi-Dee V (1995) Comprehensive site directed mutagenesis of l-2-haloacid dehalogenases to probe catalytic amino acid residues. J Biochem 117:1317–1322 Laskowski RA, MacArthur MW, Moss DS, Thornton JM (1993) PROCHECK: a program to check the stereochemical quality of protein structures. J Appl Crystallogr 26:283–291 Li YF, Hato Y, Fujii T, Hisano T, Nishihara M, Kurihara T, Esaki N (1998) Crystal structures of reaction intermediates of l-2-haloacid dehalogenase and implications for the reaction mechanism. J Biol Chem 273:15035–15044 Liu JQ, Kurihara T, Hasan KMQ, Nardi-dee V, Koshikawa N, Esaki N, Soda K (1995) Purification of thermostable and nonthermostable 2-haloacid dehalogenases with different stereospecificities from Pseudomonas sp. strain YL. J Biol Chem 270:18309–18312 Mallick P, Boutz DR, Eisenberg D, Yeates TO (2002) Genomic evidence that the intracellular proteins of archaeal microbes contain disulfide bonds. Proc Natl Acad Sci USA 99:9679–9684 Motosugi K, Esaki N, Soda K (1982) Purification and properties of a new enzyme, dl-2-haloacid dehalogenase from Pseudomonas sp. J Bacteriol 150:522–527 Murshudov GN, Vagin AA, Dodson EJ (1997) Refinement of macromolecular structures by the maximum-likelihood method. Acta Cryst D 53:240–255 Otwinowski Z, Minor W (1997) Processing of X-ray diffraction data collected in oscullation mode. Methods Enzymol 276:307–326 Pace CN, Scholtz JM (1998) A helix propensity scale based on experimental studies of peptides and proteins. Biophys J 75:422–427 Potterton P, McNicholas S, Krissinel E, Gruber J, Cowtan K, Emsley P, Murshudov GN, Cohen S, Perrakis A, Noble M (2004) Developments in the CCP4 molecular-graphics project. Acta Cryst D 60:2288–2294 Ridder IS, Rozeboom HJ, Kalk KH, Dijkstra BW (1997) Three-dimensional structure of l-2-haloacid dehalogenases from Xanthobacter autotrophicus GJ10 complexed with the substrate analogue formate. J Biol Chem 272:33015–33022 Ridder IS, Rozeboom HJ, Kalk KH, Dijkstra BW (1999) Crystal structures of intermediates in the dehalogenation of haloalkanoates by l-2-haloacid dehalogenase. J Biol Chem 274:30672–30678 Rye CA, Isupov MN, Lebedev AA, Littlechild JA (2007) An order-disorder twin crystal of l-2-haloacid dehalogenase from Sulfolobus tokodaii. Acta Cryst D 63:926–930 Slater JH (1982) New microbes to tackle toxic compounds. South Af J Sci 78:101–104 Slater JH, Bull AT, Hardman DJ (1997) Microbial dehalogenation of halogenated alkanoic acids, alcohols and alkanes. Adv Microbiol Physiol 38:133–176 Tsang JSH, Sam L (1999) Cloning and characterisation of a cryptic haloacid dehalogenases from Burkholderia cepacia MBA4. J Bacteriol 181:6003–6009 Vagin AA, Teplyakov A (1997) MOLREP: an automated program for molecular replacement. J Appl Crystallogr 30:1022–1025 van der Ploeg J, van Hall G, Janssen DB (1991) Characterization of the haloacid dehalogenase from Xanthobacter autotrophicus GJ10 and sequencing of the DhlB gene. J Bacteriol 173:7925–7933 Vriend G (1990) WHAT IF: a molecular modeling and drug design program. J Mol Graph 8:52–56