Organophosphate-degrading metallohydrolases: Structure and function of potent catalysts for applications in bioremediation

Schenk, Gerhard; Mateen, Irsa; Ng, Tee-Kheang; Mitić, Nataša; Jafelicci, Miguel; Marques, Rodrigo Fernando Costa; Gahan, Lawrence R.; Ollis, David L.

doi:10.1016/j.ccr.2016.03.006

Cited by 86 publications

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References 175 publications

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“…

Purple acid phosphatases( PAPs) are members of the large family of metallohydrolases, ag roup of enzymes that perform aw ide range of biological functions, while employing ah ighly conserved catalytic mechanism. [5][6][7] PAPs, the only known metallohydrolases that require ah eterovalent Fe III M II center (with M = Fe, Zn or Mn) for catalytic activity, have been characterized from various mammals, plants and fungi. The majority of metallohydrolases use am etalbound hydroxide to initiate catalysis, which leads to the formation of ap roposed five-coordinate oxyphosphorane species in the transition state.

…”

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confidence: 99%

The Binding Mode of an ADP Analogue to a Metallohydrolase Mimics the Likely Transition State

et al. 2019

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Purple acid phosphatases( PAPs) are members of the large family of metallohydrolases, ag roup of enzymes that perform aw ide range of biological functions, while employing ah ighly conserved catalytic mechanism. PAPs are found in plants,a nimals and fungi;i nh umans they play an important role in bone turnovera nd are thus of interest for developingt reatments for osteoporosis. The majority of metallohydrolases use am etalbound hydroxide to initiate catalysis, which leads to the formation of ap roposed five-coordinate oxyphosphorane species in the transition state. In this work, we crystallized PAPf rom red kidney beans (rkbPAP) in the presence of both adenosine and vanadate. The in crystallo-formed vanadate analogue of ADP provides detailed insight into the binding mode of aP AP substrate, captured in as tructure that mimics the putative fivecoordinate transition state. Our observations not only provide unprecedented insightinto the mechanism of metallohydrolases, but might also guide the structure-based design of inhibitors for application in the treatment of severalhuman illnesses.Metallohydrolases form al arge familyo fm ostly bimetallic enzymes that use metal ionst oactivate both the nucleophile and scissile bond of various phosphate or amide substrates. [1][2][3][4] Examples include the antibiotic-degrading metallo-b-lactamases, pesticide-decontaminating organophosphate hydrolases, and purple acid phosphatases (PAPs). [5][6][7] PAPs, the only known metallohydrolases that require ah eterovalent Fe III M II center (with M = Fe, Zn or Mn) for catalytic activity, have been characterized from various mammals, plants and fungi. [2,5] Mostp lant PAPs use either Zn II or Mn II ,w hereas their mammalianc ounterparts employ ar edox-activei ron ( Figure 1). [8,9] The reported substrates for PAPs include adenosine 5'-triphosphate (ATP), adenosine 5'-diphosphate( ADP), phosphotyrosine and pyrophosphate. [5,10] The synthetic substrate para-nitrophenyl phosphate (pNPP) is frequently used for functionalstudies. [2,5] The biological functions of PAPs are diverse and dependent on the organism. For mammals, experiments with transgenic mice have demonstrated that PAPp lays an important role in bone metabolism. [11,12] In plants, PAPs playamajor role in the acquisition of phosphorus, especially if there is al imited supplyo fp hosphate. [13,14] Due to their diverse roles, PAPs have attracted attention either as targetsf or new treatments of osteoporosis or for applicationsi na griculture to aid nutrient uptake by crops. [11,15] PAPs operate optimally in the pH range between5 .0 and 6.5, and are characterized by ad istinct purple color due to ac harge-transfer transition between an active-site tyrosine ligand and an Fe III ion. [16,17] The crystal structures of several mammalian and plant PAPs have demonstrated that, despite the difference in the metal ion selectivity and the limited degree of sequence similarity,t heir actives ite geometries are highly conserved (Figure1). [18][19][20][21][22][23] Consequently,t he proposed mod...

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“…

Purple acid phosphatases( PAPs) are members of the large family of metallohydrolases, ag roup of enzymes that perform aw ide range of biological functions, while employing ah ighly conserved catalytic mechanism. [5][6][7] PAPs, the only known metallohydrolases that require ah eterovalent Fe III M II center (with M = Fe, Zn or Mn) for catalytic activity, have been characterized from various mammals, plants and fungi. The majority of metallohydrolases use am etalbound hydroxide to initiate catalysis, which leads to the formation of ap roposed five-coordinate oxyphosphorane species in the transition state.

…”

mentioning

confidence: 99%

The Binding Mode of an ADP Analogue to a Metallohydrolase Mimics the Likely Transition State

et al. 2019

Self Cite

View full text Add to dashboard Cite

Purple acid phosphatases( PAPs) are members of the large family of metallohydrolases, ag roup of enzymes that perform aw ide range of biological functions, while employing ah ighly conserved catalytic mechanism. PAPs are found in plants,a nimals and fungi;i nh umans they play an important role in bone turnovera nd are thus of interest for developingt reatments for osteoporosis. The majority of metallohydrolases use am etalbound hydroxide to initiate catalysis, which leads to the formation of ap roposed five-coordinate oxyphosphorane species in the transition state. In this work, we crystallized PAPf rom red kidney beans (rkbPAP) in the presence of both adenosine and vanadate. The in crystallo-formed vanadate analogue of ADP provides detailed insight into the binding mode of aP AP substrate, captured in as tructure that mimics the putative fivecoordinate transition state. Our observations not only provide unprecedented insightinto the mechanism of metallohydrolases, but might also guide the structure-based design of inhibitors for application in the treatment of severalhuman illnesses.Metallohydrolases form al arge familyo fm ostly bimetallic enzymes that use metal ionst oactivate both the nucleophile and scissile bond of various phosphate or amide substrates. [1][2][3][4] Examples include the antibiotic-degrading metallo-b-lactamases, pesticide-decontaminating organophosphate hydrolases, and purple acid phosphatases (PAPs). [5][6][7] PAPs, the only known metallohydrolases that require ah eterovalent Fe III M II center (with M = Fe, Zn or Mn) for catalytic activity, have been characterized from various mammals, plants and fungi. [2,5] Mostp lant PAPs use either Zn II or Mn II ,w hereas their mammalianc ounterparts employ ar edox-activei ron ( Figure 1). [8,9] The reported substrates for PAPs include adenosine 5'-triphosphate (ATP), adenosine 5'-diphosphate( ADP), phosphotyrosine and pyrophosphate. [5,10] The synthetic substrate para-nitrophenyl phosphate (pNPP) is frequently used for functionalstudies. [2,5] The biological functions of PAPs are diverse and dependent on the organism. For mammals, experiments with transgenic mice have demonstrated that PAPp lays an important role in bone metabolism. [11,12] In plants, PAPs playamajor role in the acquisition of phosphorus, especially if there is al imited supplyo fp hosphate. [13,14] Due to their diverse roles, PAPs have attracted attention either as targetsf or new treatments of osteoporosis or for applicationsi na griculture to aid nutrient uptake by crops. [11,15] PAPs operate optimally in the pH range between5 .0 and 6.5, and are characterized by ad istinct purple color due to ac harge-transfer transition between an active-site tyrosine ligand and an Fe III ion. [16,17] The crystal structures of several mammalian and plant PAPs have demonstrated that, despite the difference in the metal ion selectivity and the limited degree of sequence similarity,t heir actives ite geometries are highly conserved (Figure1). [18][19][20][21][22][23] Consequently,t he proposed mod...

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“…In terms of the reaction mechanism it has been proposed that the catalytic cycle in CpsB involves an esterolysis-initiating hydroxide nucleophile that is doubly Lewis-activated by coordination to M1 and M2. This is similar to related phosphotriesterases (5) , MBLs (15,206) , ureases (14) arginases (238) and some PAPs (161) . The presence of the third metal ion within the active site was proposed to play an important role in substrate recognition (52) .…”

Section: Active Site Structure Of Cpsbmentioning

confidence: 99%

“…The hydroxide may also act as reaction-initiating nucleophile in PAP, but other candidates are possible, depending on the metal ion composition and substrate used in the reaction (4) . In some organophosphate (OP)-degrading BMH, including the enzyme from Agrobacterium radiobacter (OpdA), the metal ion-bridging hydroxide acts as nucleophile, while a carboxylated lysine residue stabilises the active site structure (5) . In contrast to MBL or PAP, OpdA and related enzymes are rather promiscuous with respect to metal ions they require to promote catalytic activity.…”

Section: Acknowledgementsmentioning

confidence: 99%

“…However, significant variations are observed with respect to their catalytic efficiency, substrate selectivity and metal ion affinities (5,193,194) . Site-directed mutagenesis and in vitro evolution studies demonstrated that in particular two residues in the substrate binding pocket may play an important role in mediating these variations: while R254 and Y257 in OpdA are integrated into an extensive hydrogen bonding network that connects the substrate binding pocket to the metal ion center ( Figure. 3.2 A), the corresponding residues in OPH are two histidines, and no hydrogen bond network is present ( Figure 3.2 B).…”

Section: Introductionmentioning

confidence: 99%

“…Since then OPs have played a crucial role in facilitating the global expansion of agriculture, but due to their inherent toxicity they pose a considerable risk to both human and environmental health (5) . While currently no clean and effective ways for their decontamination are available, microorganisms exposed to such compounds have evolved the enzymatic machinery to utilize them as nutrients to obtain phosphorous for metabolic functions (5) . Of particular relevance are OP-degrading phosphotriesterases (PTEs), the first of which was isolated in 1973 from a strain of Flavobacterium (188) .…”

Section: Introductionmentioning

confidence: 99%

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Kinetic, mechanistic, structural and spectroscopic investigations of Bimetallic Metallohydrolases

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Organophosphates are a class of organic compounds that are important for living organisms, forming the building blocks for DNA, RNA, and some essential cofactors. Furthermore, non‐natural organophosphates are widely used in industrial applications, including as pesticides; in laundry detergents; and, unfortunately, as chemical weapons agents. In some cases, the natural degradation of organophosphates can take thousands of years; this longevity creates problems associated with handling and the storage of waste generated by such phosphate esters, in particular. Efforts to develop new catalysts for the cleavage of phosphate esters have progressed in recent decades, mainly in the area of homogeneous catalysis. In contrast, the development of heterogeneous catalysts for the hydrolysis of organophosphates has not been as prominent. Herein, examples of heterogeneous systems are described and the importance of the development of heterogeneous catalysts applicable to organophosphate hydrolysis is highlighted, shedding light on recent advances related to different solid matrices that have been employed.

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Organophosphate-degrading metallohydrolases: Structure and function of potent catalysts for applications in bioremediation

Cited by 86 publications

References 175 publications

The Binding Mode of an ADP Analogue to a Metallohydrolase Mimics the Likely Transition State

The Binding Mode of an ADP Analogue to a Metallohydrolase Mimics the Likely Transition State

Kinetic, mechanistic, structural and spectroscopic investigations of Bimetallic Metallohydrolases

Recent Advances in Heterogeneous Catalytic Systems Containing Metal Ions for Phosphate Ester Hydrolysis

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