Multi-Tasking POM Systems

Sullivan, Kevin P.; Yin, Qiushi; Collins-Wildman, Daniel L.; Tao, Meilin; Geletii, Yurii V.; Musaev, Djamaladdin G.; Lian, Tianquan; Hill, Craig L.

doi:10.3389/fchem.2018.00365

Cited by 22 publications

(17 citation statements)

References 99 publications

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“…That could be due to their high costs, challenging synthesis, broad specificities and small functioning temperature and pH ranges . Therefore, the design of efficient, environment friendly, and economical mimics of metallohydrolases is extremely beneficial . In this review, activities of two bioinspired synthetic analogues such as polyoxometalates (POMs, I P ), and 1,4,7,10‐tetraazacyclododecane (cyclen, I C ) and their analogues that similar to IDE and GpdQ lack substrate specificity are also discussed (Figure ).…”

Section: Introductionmentioning

confidence: 99%

Mechanisms of peptide and phosphoester hydrolysis catalyzed by two promiscuous metalloenzymes (insulin degrading enzyme and glycerophosphodiesterase) and their synthetic analogues

Jayasinghe‐Arachchige

Sharma

et al. 2020

WIREs Comput Mol Sci

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The hydrolysis of extremely stable peptide and phosphoester bonds by metalloenzymes is of great interest in biotechnology and industry. However, due to various shortcomings only a handful of these enzymes have been used for industrial applications. Therefore, in the last two decades intensive scientific efforts have been made in rational development of small molecules to imitate the activities of natural enzymes. Despite these efforts, their currently available synthetic analogues are inferior in terms of selectivity, catalytic rate, and turnover and the designing of efficient artificial metalloenzymes remains a distant goal. This is a challenging area of research that necessitates a rigorous integration between experiments and theory. The realization of this goal requires knowledge of the catalytic activities of both enzymes and their existing analogues and an effective fusion of that knowledge. This article reviews several studies in which a plethora of computational techniques have been successfully employed to investigate the functioning of two chemically promiscuous mono‐ and binuclear metalloenzymes (insulin degrading enzyme and glycerophosphodiesterase) and two synthetic analogues. These studies will help us derive fundamental principles of peptide and phosphoester hydrolysis and pave the way to design efficient small molecule catalysts for these reactions. This article is categorized under: Structure and Mechanism > Reaction Mechanisms and Catalysis

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Section: Introductionmentioning

confidence: 99%

Mechanisms of peptide and phosphoester hydrolysis catalyzed by two promiscuous metalloenzymes (insulin degrading enzyme and glycerophosphodiesterase) and their synthetic analogues

Jayasinghe‐Arachchige

Sharma

et al. 2020

WIREs Comput Mol Sci

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“…Although these enzymes exhibit remarkable activities, they suffer from several limitations such as undesirable selectivity, difficulties in extraction or synthesis, high cost and narrow functional temperature, and pH range (Kövári and Krämer, 1996; Cowan, 2001; Mancin et al, 2012). Therefore, in the last couple of decades, intensive efforts have been made to design small metal complexes as synthetic analogs of natural enzymes for phosphoester hydrolysis (Burstyn and Deal, 1993; Hegg and Burstyn, 1998; Komiyama and Sumaoka, 1998; Blaskó and Bruice, 1999; Williams et al, 1999; Sreedhara and Cowan, 2001; Deck et al, 2002; Mitić et al, 2006; Niittymaki and Lonnberg, 2006; Bonomi et al, 2008; Krauser et al, 2010; Mancin et al, 2012; Daver et al, 2016; Sullivan et al, 2018). These analogs can offer multiple advantages over natural enzymes in terms of cost, size, and functionality (Weston, 2005; Yoji et al, 2006).…”

Section: Introductionmentioning

confidence: 99%

Effects of the Metal Ion on the Mechanism of Phosphodiester Hydrolysis Catalyzed by Metal-Cyclen Complexes

Jayasinghe‐Arachchige

Zuchniarz

et al. 2019

Front. Chem.

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In this study, mechanisms of phosphodiester hydrolysis catalyzed by six di- and tetravalent metal-cyclen ( M-C ) complexes ( Zn-C, Cu-C, Co-C, Ce-C, Zr-C and Ti-C ) have been investigated using DFT calculations. The activities of these complexes were studied using three distinct mechanisms: (1) direct attack ( DA ), (2) catalyst-assisted ( CA ), and (3) water-assisted ( WA ). All divalent metal complexes ( Zn-C, Cu-C and Co-C ) coordinated to the BNPP substrate in a monodentate fashion and activated its scissile phosphoester bond. However, all tetravalent metal complexes ( Ce-C, Zr-C , and Ti-C ) interacted with BNPP in a bidentate manner and strengthened this bond. The DA mechanism was energetically the most feasible for all divalent M-C complexes, while the WA mechanism was favored by the tetravalent complexes, except Ce-C . The divalent complexes were found to be more reactive than their tetravalent counterparts. Zn-C catalyzed the hydrolysis with the lowest barrier among all M-C complexes, while Ti-C was the most reactive tetravalent complex. The activities of Ce-C and Zr-C , except Ti-C , were improved with an increase in the coordination number of the metal ion. The structural and mechanistic information provided in this study will be very helpful in the development of more efficient metal complexes for this critical reaction.

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“…Polyoxometalates (POMs) are a diverse class of metal-oxygen clusters with a wide range of tunable parameters such as their size, polarity, charge density, solubility and acid-strength (Pope, 1983; Long et al, 2010). Their easily modifiable properties (Sullivan et al, 2018) make them highly applicable in various research domains such as modern catalysis (Lv et al, 2012; Wang and Yang, 2015; Huang et al, 2018; Martin-Sabi et al, 2018; Yu et al, 2018), green energy production and storage (Chen et al, 2017, 2018), material science (Bijelic and Rompel, 2015; Sun et al, 2015; Boyd et al, 2017; Vilà-Nadal and Cronin, 2017; Zhan et al, 2017; Luo et al, 2018), bio-mimics design (Kulikov et al, 2017), and medicine (Bijelic et al, 2018a,b). Currently nearly 80% of all patents concerning POMs are related to catalysis, reflecting their importance as catalysts in various applications (Wang and Yang, 2015; Weinstock et al, 2018).…”

Section: Introductionmentioning

confidence: 99%

Selective Hydrolysis of Ovalbumin Promoted by Hf(IV)-Substituted Wells-Dawson-Type Polyoxometalate

et al. 2018

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The reactivity and selectivity of Wells-Dawson type polyoxometalate (POM), K16[Hf(α2-P2W17O61)2]·19H2O (Hf1-WD2), have been examined with respect to the hydrolysis of ovalbumin (OVA), a storage protein consisting of 385 amino acids. The exact cleavage sites have been determined by Edman degradation experiments, which indicated that Hf1-WD2 POM selectively cleaved OVA at eight peptide bonds: Phe13-Asp14, Arg85-Asp86, Asn95-Asp96, Ala139-Asp140, Ser148-Trp149, Ala361-Asp362, Asp362-His363, and Pro364-Phe365. A combination of spectroscopic methods including 31P NMR, Circular Dichroism (CD), and Tryptophan (Trp) fluorescence spectroscopy were employed to gain better understanding of the observed selective cleavage and the underlying hydrolytic mechanism. 31P NMR spectra have shown that signals corresponding to Hf1-WD2 gradually broaden upon addition of OVA and completely disappear when the POM-protein molar ratio becomes 1:1, indicating formation of a large POM/protein complex. CD demonstrated that interactions of Hf1-WD2 with OVA in the solution do not result in protein unfolding or denaturation even upon adding an excess of POM. Trp fluorescence spectroscopy measurements revealed that the interaction of Hf1-WD2 with OVA (Kq = 1.1 × 105 M−1) is both quantitatively and qualitatively slightly weaker than the interaction of isostructural Zr-containing Wells-Dawson POM (Zr1-WD2) with human serum albumin (HAS) (Kq = 5.1 × 105 M−1).

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Multi-Tasking POM Systems

Cited by 22 publications

References 99 publications

Mechanisms of peptide and phosphoester hydrolysis catalyzed by two promiscuous metalloenzymes (insulin degrading enzyme and glycerophosphodiesterase) and their synthetic analogues

Mechanisms of peptide and phosphoester hydrolysis catalyzed by two promiscuous metalloenzymes (insulin degrading enzyme and glycerophosphodiesterase) and their synthetic analogues

Effects of the Metal Ion on the Mechanism of Phosphodiester Hydrolysis Catalyzed by Metal-Cyclen Complexes

Selective Hydrolysis of Ovalbumin Promoted by Hf(IV)-Substituted Wells-Dawson-Type Polyoxometalate

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