Wikipedia

Organophosphorus acid anhydrolase

Organophosphorus acid anhydrolase (OPAA) is an enzyme that been shown to be particularly effective in detoxifying organophosphorus-containing compounds, such as deadly nerve gas used in chemical warfare.[1] The enzyme is found in a diverse range of organisms, including protozoa,[2] squid and clams,[3] mammals,[4] and soil bacteria.[5] A highly active form of the enzyme is typically isolated from the marine bacteria Alteromonas undina for laboratory study.[6] This form is both halophilic and thermophilic, making it particularly useful for detoxification applications. A slightly less active variant of OPAA has also been isolated in mung beans and slime mold duckweed.[7]

Enzyme mechanism

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Figure 1: OPAA reaction mechanism

Although the exact mechanism of OPAA’s nerve-agent detoxification is unclear, researchers have deduced that the basic reaction follows a general base mechanism with a simple in-line displacement of fluoride at the phosphorus center using an activated water molecule, as seen in Figure 1.[8]

OPAA activity is enhanced by reducing agents such as dithiothreitol (DTT) and beta-mercaptoethanol.[9] OPAA is also catalytically active over a wide pH range between 6.5 and 9.5 and temperature range between 10 and 65 °C, and is stimulated by manganese.[10]

Enzyme structure

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Figure 2: OPAA trimer

OPAA is a single polypeptide composed of 517 amino acids, with a molecular weight of 58 kDa.[11][12] The three-dimensional crystal structure of OPAA is a trimer, as seen in Figure 2. The enzyme has a 22% amino acid homology with human prolidase and a 30% homology to E. coli aminopeptidase P.[12]

The enzyme is unstable under harsh conditions, losing its activity in the presence of organic solvents, at elevated temperature, and over long-term storage.[1] Unprotected OPAA enzymes are also vulnerable to inhibition from other enzymes.[1]

Biological function

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The native biological role of OPAAs remains unknown. Its similarity to prolidase has led some researchers to theorize that it may be involved in cellular dipeptide metabolism, although conclusions about its true function remains elusive.[9][12]

Industrial relevance

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OPAA’s susbstrate-specificity to organophosphorus-containing compounds, especially fluoride-containing G-type nerve agents such as sarin, cyclosarin, tabun, and soman,[13][14] have drawn the interest of the U.S. Army . That attention has resulted in the establishment of a biodegradation program in search of safe and effective means of disposal for chemical weapons in the 1980s; the program is currently called the Advanced Catalytic Enzyme System (ACES).[15]

References

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  1. ^ a b c Hoskin, F. C. G.; Rousch, A. H. (1982). "Hydrolysis of nerve gas by squid type diisopropylphosphorofluoridate hydrolyzing enzyme on agarose resin". Science. 215 (4537): 1255–1257. Bibcode:1982Sci...215.1255H. doi:10.1126/science.7058344. PMID 7058344.
  2. ^ Landis, W. G.; Durst, H. D.; Savage Jr., R. E.; Haley, D. M.; Haley, M. V.; Johnson, D. W. (1987). "Discovery of multiple organofluorophosphate hydrolyzing activities in the protozoan Tetrahymena thermophila". J. Appl. Toxicol. 7 (1): 35–41. doi:10.1002/jat.2550070107. PMID 3611595. S2CID 9077312.
  3. ^ Anderson, R. S.; Durst, H. D.; Landis, W. G. (1988). "Initial characterization of the organophosphate acid anhydrase activity in the clam, Rangia cuneata". Comp. Biochem. Physiol. 91C: 575–578.
  4. ^ Little, J. S., C. A. Broomfield, L. J. Boucher, and M. K. Fox-Talbot. 1986. Partial characterization of a rat liver enzyme that hydrolyzes sarin, soman, tabun and DFP. Fed. Proc. 45:791.
  5. ^ DeFrank, J. J.; Cheng, T.-C. (1991). "Purification and properties of an organophosphorus acid anhydrase from a halophilic bacterial isolate". J. Bacteriol. 173 (6): 1938–1943. doi:10.1128/jb.173.6.1938-1943.1991. PMC 207724. PMID 2001997.
  6. ^ Cheng, T.; Harvey, S.; Stroup, A. (1993). "Purification and properties of a highly active organophosphorus acid anhydrolase from alteromonas undina". Applied and Environmental Microbiology. 59 (9): 3138–3140. Bibcode:1993ApEnM..59.3138C. doi:10.1128/AEM.59.9.3138-3140.1993. PMC 182420. PMID 16349054.
  7. ^ Hoskin, F.; Walker, J.; Mello, C. (1999). "Organophosphorus acid anhydrolase in slime mold duckweed and mung bean: a continuing search for a physiological role and a natural substrate". Chemico-Biological Interactions. 119–120: 399–404. doi:10.1016/S0009-2797(99)00051-4. PMID 10421476.
  8. ^ Dumas, DP; Caldwell, SR; Wild, JR; Raushel, FM (1989). "Purification and Properties of the Phosphotriesterase from Pseudomonas diminuta". Journal of Biological Chemistry. 264 (33): 19659–19665. doi:10.1016/S0021-9258(19)47164-0. PMID 2555328.
  9. ^ a b Elashvili, I, DeFrank, JJ, and Culotta, VC, Purification and characterization of DFPase from Alteromonas haloplanktis ATCC 14393, Proceedings of the 1998 ERDEC Scientific Conference on Chemical and Biological Defense Research, 17–20 November 1998, AD-A375 171.
  10. ^ Lewis, VE; Donarski, WJ; Wild, JR; Raushel, FM (1988). "Mechanism and Stereochemical course at phosphorus of the reaction catalyzed by a bacterial phosphotriesterase". Biochemistry. 27 (5): 1591–1597. doi:10.1021/bi00405a030. PMID 2835095.
  11. ^ Cheng, T-c, Harvey, SP, and Chen, GL, Cloning and Expression of a Gene Encoding a Bacterial Enzyme for Decontamination of Organophosphorus Nerve Agents and Nucleotide Sequence of the Enzyme, Applied and Environmental Microbiology, 62 (1996) 1636-1641.
  12. ^ a b c Cheng, T-c, Liu, L, DeFrank, JJ, Anderson, D, and Hamilton, AB, Bacterial Nerve Agent Degrading Enzymes that are Similar to Prolidase Protein Sequence and Activity, Proceedings of the 1995 ERDEC Scientific Conference on Chemical Defense Research, 14–17 November 1995, AD-A315 812.
  13. ^ Cheng,T-c and Calomiris, JJ Stability of a nerve-agent-degrading enzyme in blast containment and firefighting foams, Proceedings of the 1994 ERDEC Scientific Conference on Chemical Defense Research, 15–18 November 1994, ADE 479952-001
  14. ^ Cheng, T-c, DeFrank, JJ, Rastogi, VK, Alteromonas prolidase for the organophosphorus G-agent decontamination, Chemico-Biological Interactions 119-120(1999) 455-462.
  15. ^ DeFrank, JJ, Cheng, T-c, Harvey, SP, and Rastogi, VK, Advanced catalytic enzyme system (ACES)-dual use capabilities, Proceedings of the 2002 Joint Service Scientific Conference on Chemical & Biological Defense Research, 19–21 November 2002, AD-M001 523.
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