Comparative analysis of the metal-dependent structural and functional properties of mouse and human SMP30

Dutta, Roshan Kumar; Parween, Fauzia; Hossain, Md. Summon; Dhama, Nidhi; Pandey, Parmanand; Gupta, Rinkoo Devi

doi:10.1371/journal.pone.0218629

Cited by 9 publications

(6 citation statements)

References 29 publications

(33 reference statements)

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“…In addition to the above described enzymes, several proteins have been shown to possess a moonlighting OP hydrolyzing activity. For instance, senescence marker protein (SMP30) isolated from mouse liver cytosol, is capable of hydrolyzing DFP and other OPs such as sarin, soman, and tabun (Scott and Bahnson, 2011; Dutta et al, 2019). Although SMP30 can hydrolyze similar substrates like DFPase, it is not a calcium binding protein, and shows activity in the presence of Mg 2+ and Mn 2+ (Dutta et al, 2019).…”

Section: Enzymes For Decontaminationmentioning

confidence: 99%

“…For instance, senescence marker protein (SMP30) isolated from mouse liver cytosol, is capable of hydrolyzing DFP and other OPs such as sarin, soman, and tabun (Scott and Bahnson, 2011; Dutta et al, 2019). Although SMP30 can hydrolyze similar substrates like DFPase, it is not a calcium binding protein, and shows activity in the presence of Mg 2+ and Mn 2+ (Dutta et al, 2019). Bacterial lactonases have also shown potential as OP-degrading enzymes due to their high degree of substrate promiscuity (Draganov, 2010).…”

Section: Enzymes For Decontaminationmentioning

confidence: 99%

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Enzymatic Bioremediation of Organophosphate Compounds—Progress and Remaining Challenges

Thakur

Medintz

Walper

2019

Front. Bioeng. Biotechnol.

102

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Organophosphate compounds are ubiquitously employed as agricultural pesticides and maintained as chemical warfare agents by several nations. These compounds are highly toxic, show environmental persistence and accumulation, and contribute to numerous cases of poisoning and death each year. While their use as weapons of mass destruction is rare, these never fully disappear into obscurity as they continue to be tools of fear and control by governments and terrorist organizations. Beyond weaponization, their wide-scale dissemination as agricultural products has led to environmental accumulation and intoxication of soil and water across the globe. Therefore, there is a dire need for rapid and safe agents for environmental bioremediation, personal decontamination, and as therapeutic detoxicants. Organophosphate hydrolyzing enzymes are emerging as appealing targets to satisfy decontamination needs owing to their ability to hydrolyze both pesticides and nerve agents using biologically-derived materials safe for both the environment and the individual. As the release of genetically modified organisms is not widely accepted practice, researchers are exploring alternative strategies of organophosphate bioremediation that focus on cell-free enzyme systems. In this review, we first discuss several of the more prevalent organophosphorus hydrolyzing enzymes along with research and engineering efforts that have led to an enhancement in their activity, substrate tolerance, and stability. In the later half we focus on advances achieved through research focusing on enhancing the catalytic activity and stability of phosphotriesterase, a model organophosphate hydrolase, using various approaches such as nanoparticle display, DNA scaffolding, and outer membrane vesicle encapsulation.

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Section: Enzymes For Decontaminationmentioning

confidence: 99%

Section: Enzymes For Decontaminationmentioning

confidence: 99%

Enzymatic Bioremediation of Organophosphate Compounds—Progress and Remaining Challenges

Thakur

Medintz

Walper

2019

Front. Bioeng. Biotechnol.

102

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“…SMP30 is abundantly expressed in kidney proximal tubule cells, and its expression decreases with age. Loss of SMP30 is associated with kidney damage in several mouse models ( Yumura et al., 2006 ; Kondo et al., 2013 ; Miyata et al., 2013 ; Okada et al., 2015 ; Kondo and Ishigami, 2016 ; Yamauchi et al., 2016 ; Dutta et al., 2019 ). However, we did not find reduced SMP30 expression in mouse kidney and NRK cells.…”

Section: Discussionmentioning

confidence: 99%

High Phosphate Induces and Klotho Attenuates Kidney Epithelial Senescence and Fibrosis

et al. 2020

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Cellular senescence is an irreversible cell growth arrest and is associated with aging and age-related diseases. High plasma phosphate (Pi) and deficiency of Klotho contribute to aging and kidney fibrosis, a pathological feature in the aging kidney and chronic kidney disease. This study examined the interactive role of Pi and Klotho in kidney senescence and fibrosis. Homozygous Klotho hypomorphic mice had high plasma Pi, undetectable Klotho in plasma and kidney, high senescence with massive collagen accumulation in kidney tubules, and fibrin deposits in peritubular capillaries. To examine the Pi effect on kidney senescence, a high (2%) Pi diet was given to wild-type mice. One week of high dietary Pi mildly increased plasma Pi, and upregulated kidney p16/p21 expression, but did not significantly decrease Klotho. Two weeks of high Pi intake led to increase in plasminogen activator inhibitor (PAI)-1, and decrease in kidney Klotho, but still without detectable increase in kidney fibrosis. More prolonged dietary Pi for 12 weeks exacerbated kidney senescence and fibrosis; more so in heterozygous Klotho hypomorphic mice compared to wild-type mice, and in mice with chronic kidney disease (CKD) on high Pi diet compared to CKD mice fed a normal Pi diet. In cultured kidney tubular cells, high Pi directly induced cellular senescence, injury and epithelialmesenchymal transition, and enhanced H 2 O 2-induced cellular senescence and injury, which were abrogated by Klotho. Fucoidan, a bioactive molecule with multiple biologic functions including senescence inhibition, blunted Pi-induced cellular senescence, oxidation, injury, epithelial-mesenchymal transition, and senescence-associated secretary phenotype. In conclusion, high Pi activates senescence through distinct but interconnected mechanisms: upregulating p16/p21 (early), and elevating plasminogen activator inhibitor-1 and downregulating Klotho (late). Klotho may be a promising agent to attenuate senescence and ameliorate age-associated, and Pi-induced kidney degeneration such as kidney fibrosis.

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“…In humans, it is located at p11.3-q11.2 of the X chromosome [ 114 ]. Like PON1, it has also been reported to show lactonase [ 116 ] activity as its physiological function; however, it also catalyses the hydrolysis of an OPC, diisopropyl fluorophosphate, thus acting as DFPase [ 117 ]. SMP30 is also referred to as regucalcin due to its high affinity with calcium indicating its role in maintaining calcium homeostasis in the cells [ 118 – 120 ].…”

Section: Treatment Strategies For Organophosphorus Poisoningmentioning

confidence: 99%

“…These analyses suggest that SMP30 might play an important role in calcium homeostasis and providing protection against OPC poisoning in human. A recent study from our research group demonstrated that both mouse and human SMP30 showed organophosphate hydrolase activity in the presence of Ca 2+ and Zn 2+ , thus displaying metal-dependent promiscuous activity [ 116 ]. A recombinant HuSMP30 has also been expressed with chaperones as a soluble protein and has been characterized for its DFPase activity [ 122 ].…”

Section: Treatment Strategies For Organophosphorus Poisoningmentioning

confidence: 99%

Organophosphorus Nerve Agents: Types, Toxicity, and Treatments

Mukherjee

Gupta

2020

Journal of Toxicology

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Organophosphorus compounds are extensively used worldwide as pesticides which cause great hazards to human health. Nerve agents, a subcategory of the organophosphorus compounds, have been produced and used during wars, and they have also been used in terrorist activities. These compounds possess physiological threats by interacting and inhibiting acetylcholinesterase enzyme which leads to the cholinergic crisis. After a general introduction, this review elucidates the mechanisms underlying cholinergic and noncholinergic effects of organophosphorus compounds. The conceivable treatment strategies for organophosphate poisoning are different types of bioscavengers which include stoichiometric, catalytic, and pseudocatalytic. The current research on the promising treatments specifically the catalytic bioscavengers including several wild-type organophosphate hydrolases such as paraoxonase and phosphotriesterase, phosphotriesterase-like lactonase, methyl parathion hydrolase, organophosphate acid anhydrolase, diisopropyl fluorophosphatase, human triphosphate nucleotidohydrolase, and senescence marker protein has been widely discussed. Organophosphorus compounds are reported to be the nonphysiological substrate for many mammalian organophosphate hydrolysing enzymes; therefore, the efficiency of these enzymes toward these compounds is inadequate. Hence, studies have been conducted to create mutants with an enhanced rate of hydrolysis and high specificity. Several mutants have been created by applying directed molecular evolution and/or targeted mutagenesis, and catalytic efficiency has been characterized. Generally, organophosphorus compounds are chiral in nature. The development of mutant enzymes for providing superior stereoselective degradation of toxic organophosphorus compounds has also been widely accounted for in this review. Existing enzymes have shown limited efficiency; hence, more effective treatment strategies have also been critically analyzed.

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Comparative analysis of the metal-dependent structural and functional properties of mouse and human SMP30

Cited by 9 publications

References 29 publications

Enzymatic Bioremediation of Organophosphate Compounds—Progress and Remaining Challenges

Enzymatic Bioremediation of Organophosphate Compounds—Progress and Remaining Challenges

High Phosphate Induces and Klotho Attenuates Kidney Epithelial Senescence and Fibrosis

Organophosphorus Nerve Agents: Types, Toxicity, and Treatments

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