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Advances in research on haloalkane dehalogenases and its sulfur mustard degradation function(PDF)

Chinese Journal of Applied & Environmental Biology[ISSN:1006-687X/CN:51-1482/Q]

2015 05
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Advances in research on haloalkane dehalogenases and its sulfur mustard degradation function
XI Hailing LIU Changcai WEN Xianfang CHEN Likun
State Key Laboratory of NBC Protection for Civilian, Beijing 102205, China
haloalkane dehalogenases blister agents catalytic hydrolysis decontamination crystal structure catalytic hydrolysis mechanism
X172 : Q55

Sulfur Mustard (bis-(2-chloroethyl) sulphide, HD), also known as yperite, is one of the most important blister agents. It could react with a large number of biological molecules with a strong cytotoxicity effect, resulting in blistering, erosion and necrosis of the skin and various tissues. Recently, several classes of microbial enzymes have been found to be able to degrade HD with high catalytic activity but no disadvantages of the common chemical decontamination of HD. Haloalkane dehalogenases (HLDs, EC3.8.1.5) draws great research attention for environmentally friendly decontaminating HD with only nontoxic thiodiglycol produced. In order to provide theoretical reference basis for enzymatic decontamination of HD, this paper reviews the observation and evolutionary relationship, structures, substrate specificities, catalytic properties and potential applications of these HLDs with high catalytic hydrolysis of HD. The analysis shows that these HLDs belonging to the same subfamily have different substrate specificities but similar spatial structures of the catalytic triad contributing to the common SN2 nucleophilic substitution reaction mechanism for catalytic hydrolysis of HD. The paper also suggests that the problems on improving poor stability of HLDs and efficiency of catalytic hydrolysis of HD should be addressed by methods of molecular biology, genetic engineering and immobilized techniques.


1 Borak J, Sidell FR. Agents of chemical warfare: sulfur mustard [J]. Ann Emerg Med, 1992, 21: 303-308
2 Reiter G, Mueller S, Koller M, Thiermann H, WorekBundeswehr F. In vitro toxicokinetic studies of cyclosarin: Molecular mechanisms of elimination [J]. Toxicol Lett, 2014, 227: 1-11
3 习海玲, 赵三平, 周文. 基于过氧化物的消毒技术研究进展[J]. 环境科学, 2013, 34: 1645-1652 [Xi HL, Zhao SP, Zhou W. Advances in peroxide-based decontaminating technologies [J]. Environ Sci, 2013, 34: 1645-1652]
4 赵三平, 习海玲, 左言军, 王琦. Na2MoO4催化H2O2氧化芥子气模拟剂苯甲硫醚的动力学与产物[J]. 分子催化, 2015, 29 (1): 45-51 [Zhao SP, Xi HL, Zuo YJ, Wang X. Oxidation kinetics and products of methyl phenyl sulfide, a sulfur mustard simulant by sodium molybdate catalyzed hydrogen peroxide solution. J Mol Catal (China), 2015, 29 (1): 45-51]
5 习海玲, 孔令策. 国外人员应急洗消技术现状与发展趋势[C]//中国化学会. 公共安全中的化学问题研究进展(第二卷). 北京: 中国人民公安大学出版社, 2011 [Xi HL, Kong LC. Research status and development trend of emergency decontamination technology for personnel [C]//Chinese Chemical Society. Research Progress on Chemical Problems in Public Safety (2nd volumes). Beijing: Chinese People’s Public Security University Press , 2011]
6 Han ST, Li J, Xi HL, Xu DN, Zuo YJ, Zhang JH. Photocatalytic decomposion of acephate in irradiated TiO2 suspensions [J]. J Hazard Mater, 2009, 163: 1165-1172
7 Han ST, Zhang GY, Xi HL, Xu DN, Fu XZ, Wang XX. Sulfated TiO2 decontaminate 2-CEES and DMMP in vapor phase [J]. Catal Lett, 2008, 122: 106-110
8 习海玲, 刘昌财, 问县芳, 赵三平. 磷酸三酯水解酶空间结构及催化水解机理研究进展[J]. 应用与环境生物学报, 2015, 21 (1): 1-23 [Xi HL, Liu CC, Wen XF, Zhao SP. Advance on three-dimensional spatial structure and catalytic mechanisms for phosphoric triester hydrolase [J]. Chin J Appl Environ Biol, 2015, 21 (1): 1-23]
9 问县芳, 习海玲, 陈立坤, 管臣, 罗伟清. 有机磷神经毒剂降解酶研究进展[J]. 广州化工, 2010, 38: 66-69 [Wen XF, Xi HL, Chen LK, Guan C, Luo WQ. Advances on organophosphorus nerve agents degradation [J]. Guangzhou Chem Ind, 2010, 38: 66-69]
10 问县芳, 袁永泽, 习海玲, 钟近艺, 陈立坤, 王攀, 肖文精, 刘德立. 一种新型有机磷降解酶的二异丙基氟磷酸酯水解特性研究[J]. 华中师范大学学报: 自然科学版, 2013, 1: 53-56 [Wen XF, Yuan YZ, Xi HL, Zhong JY, Chen LK, Wang P, Xiao WJ, Liu DL. Characteristics of a novel organophosphorus pesticide-degrading enzyme on diisopropyl fluorophosphates. J Huazhong Norm Univ (Nat Sci), 2013, 1: 53-56]
11 Franken SM, Rozeboom HJ, Kalk KH, Dijkstra BW. Crystal structure of haloalkane dehalogenase: an enzyme to detoxify halogenated alkanes [J]. EMBO J, 1991, 10: 1297-1302
12 Dijkstra BBW. Crystallographic analysis of the catalytic mechanism of haloalkane dehalogenase [J]. Nature, 1993, 363: 693-698.
13 Pries F, Kingma J, Pentenga M, van Pouderoyen G, Jeronimus-Stratingh CM, Bruins AP, Janssen DB. Site-directed mutagenesis and oxygen isotope incorporation studies of the nucleophilic aspartate of haloalkane dehalogenase [J]. Biochemistry, 1994, 33: 1242-1247
14 Verschueren KH, Seljee F, Rozeboom HJ, Kalk KH, Dijkstra BW. Crystallographic analysis of the catalytic mechanism of haloalkane dehalogenase [J]. Nature, 1993, 363: 693-698
15 Koudelakova T, Bidmanova S, Dvorak P, Pavelka A, Chaloupkova R, Prokop Z, Damborsky J. Haloalkane dehalogenases: biotechnological applications [J]. Biotechnol J, 2013, 8: 32-45
16 李安章, 邵宗泽. 微生物卤代烷烃脱卤酶研究进展[J]. 微生物学报, 2015, 55: 381-388 [Li AZ, Shao ZZ. Research progress of microbial haloalkane dehalogenase - a review [J]. Acta Microbiol Sin, 2015, 55: 381-388]
17 Keuning S, Janssen DB, Witholt B. Purification and characterization of hydrolytic haloalkane dehalogenase from Xanthobacter autotrophicus GJ10 [J]. J Bacteriol, 1985, 163: 635-639
18 Nagata Y, Miyauchi K, Damborsky J, Manova K, Ansorgova A, Takagi M. Purification and characterization of a haloalkane dehalogenase of a new substrate class from a gamma-hexachlorocyclohexane-degrading bacterium, Sphingomonas paucimobilis UT26 [J]. Appl Environ Microbiol, 1997, 63: 3707-3710
19 Nagata Y, Nariya T, Ohtomo R, Fukuda M, Yano K, Takagi M. Cloning and sequencing of a dehalogenase gene encoding an enzyme with hydrolase activity involved in the degradation of gamma-hexachlorocyclohexane in Pseudomonas paucimobilis [J]. J Bacteriol, 1993, 175: 6403-6410
20 Kulakova AN, Larkin MJ, Kulakov LA. The plasmid-located haloalkane dehalogenase gene from Rhodococcus rhodochrous NCIMB 13064 [J]. Microbiol, 1997, 143: 109-115
21 Sato Y, Natsume R, Tsuda M, Damborsky J, Nagata Y, Senda T. Crystallization and preliminary crystallographic analysis of a haloalkane dehalogenase, DbjA, from Bradyrhizobium japonicum USDA110 [J]. Acta Crystallogr Sect F: Struct Biol Cryst Commun, 2007, 63: 294-296
22 Pavlova M, Klvana M, Jesenska A, Prokop Z, Konecna H, Sato T, Tsuda M, Nagata Y, Damborsky J. The identification of catalytic pentad in the haloalkane dehalogenase DhmA from Mycobacterium avium N85: reaction mechanism and molecular evolution [J]. J Struct Biol, 2007, 157: 384-392
23 Jesenska A, Bartos M, Czernekova V, Rychlik I, Pavlik I, Damborsy J. Cloning and expression of the haloalkane dehalogenase gene dhmA from Mycobactetium avium N85 and preliminary characterization of DhmA [J]. Appl Environ Microbiol, 2002, 68: 3724-3730
24 Meyer T, Burow M, Bauer M, Papenbrock J. Arabidopsis sulfurtransferases: investigation of their function during senescence and in cyanide detoxification [J]. Planta, 2003, 217: 1-10
25 Jesenska A, Monincova M, Koudelakova T, Hasan K, Chaloupkova R, Prokop Z, Geerlof A, Damborsky J. Biochemical characterization of haloalkane dehalogenases DrbA and DmbC, representatives of a novel subfamily [J]. Appl Environ Microbiol, 2009, 75: 5157-5160
26 Bogdanovic X, Hesseler M, Palm GJ, Bornscheuer UT, Hinrichs W. Crystallization and preliminary X-ray diffraction studies of the putative haloalkane dehalogenase DppA from Plesiocystis pacifica SIR-I [J]. Acta Crystallogr Sect F: Struct Biol Cryst Commun, 2010, 66: 828-830
27 Li A, Shao Z. Biochemical characterization of a haloalkane dehalogenase DadB from Alcanivorax dieselolei B-5 [J]. PLoS ONE, 2014, 9: e89144
28 Prudnikova T, Mozga T, Rezacova P, Chaloupkova R, Sato Y, Nagata Y, Brynda J, Kuty M, Damborsky J, Smatanova IK. Crystallization and preliminary X-ray analysis of a novel haloalkane dehalogenase DbeA from Bradyrhizobium elkani USDA94 [J]. Acta Crystallogr Sect F: Struct Biol Cryst Commun, 2009, 65: 353-356
29 Hasan K, Fortova A, Koudelakova T, Chaloupkova R, Ishitsuka M, Nagata Y, Damborsky J, Prokop Z. Biochemical characteristics of the novel haloalkane dehalogenase DatA, isolated from the plant pathogen Agrobacterium tumefaciens C58 [J]. Appl Environ Microbiol, 2011, 77: 1881-1884
30 Hesseler M, Bogdanovic X, Hidalgo A, Berenguer J, Palm GJ, Hinrichs W, Bornscheuer UT. Cloning, functional expression, biochemical characterization, and structural analysis of a haloalkane dehalogenase from Plesiocystis pacifica SIR-1 [J]. Appl Environ Microbiol, 2011, 91: 1049-1060
31 Oakley AJ, Prokop Z, Bohac M, Kmunicek J, Jedlicka T, Monincova M, Kuta-Smatanova I, Nagata Y, Damborsky J, Wilce MCJ. Exploring the structure and activity of haloalkane dehalogenase from Sphingomonas paucimobilis UT26: evidence for product- and water-mediated inhibition [J]. Biochemistry, 2002, 41: 4847-4855
32 Newman J, Peat TS, Richard R, Kan L, Swanson PE, Affholter JA, Holmes IH, Schindler JF, Unkefer CJ, Terwilliger TC. Haloalkane dehalogenases: structure of a Rhodococcus enzyme [J]. Biochem, 1999, 38: 16105-16114
33 Prokop Z, Sato Y, Brezovsky J, Mozga T, Chaloupkova R, Koudelakova T, Jerabek P, Stepankova V, Natsume R, van Leeuwen JGE, Janssen DB, Florian J, Nagata Y, Senda T, Damborsky J. Enantioselectivity of haloalkane dehalogenases and its modulation by surface loop engineering [J]. Angew Chem Int Ed, 2010, 49: 6111-6115
34 Zhang X, Wang H, Yang C, Du D, Lin Y. Preparation, characterization of Fe3O4 at TiO2 magnetic nanoparticles and their application for immunoassay of biomarker of exposure to organophosphorus pesticides [J]. Biosensors Bioelectron, 2013, 41: 669-674
35 Mazumdar PA, Hulecki JC, Cherney MM, Garen CR, James MNG. X-ray crystal structure of Mycobacterium tuberculosis haloalkane dehalogenase Rv2579 [J]. Biochim Biophys Acta-Proteins Proteomics, 2008, 1784: 351-362
36 Koudelakova T, Chovancova E, Brezovsky J, Monincova M, Fortova A, Jarkovsky J, Damborsky J. Substrate specificity of haloalkane dehalogenases [J]. Biochem J, 2011, 435: 345-354
37 Prokop Z, Oplu?til F, DeFrank J, Damborsk? J. Enzymes fight chemical weapons [J]. Biotech J, 2006, 1: 1370-1380
38 Pieters RJ, Spelberg JHL, Kellogg RM, Janssen DB. The enantioselectivity of haloalkane dehalogenases [J]. Tetrahedron Lett, 2001, 42: 469-471
39 Black RM, Clarke RJ, Read RW, Reid MT. Application of gas chromatography-mass spectrometry and gas chromatography-tandem mass spectrometry to the analysis of chemical warfare samples, found to contain residues of the nerve agent sarin, sulphur mustard and their degradation products [J]. J Chromatogr A, 1994, 662: 301-321
40 Verschueren KH, Franken SM, Rozeboom HJ, Kalk KH, Dijkstra BW. Refined X-ray structures of haloalkane dehalogenase at pH 6.2 and pH 8.2 and implications for the reaction mechanism [J]. J Mol Biol, 1993, 232: 856-872
41 Janssen DB. Evolving haloalkane dehalogenases [J]. Curr Opin Chem Biol, 2004, 8: 150-159


Last Update: 2015-10-29