Alternate‐Site Enzyme Promiscuity

Taglieber, Andreas; Höbenreich, Horst; Carballeira, José Daniel; Mondière, Régis; Reetz, Manfred T.

doi:10.1002/anie.200702751

Cited by 58 publications

(18 citation statements)

References 48 publications

(11 reference statements)

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“…Therefore, it appears that the gene family model described for FLS, with one catalytically active member and several pseudogenes, may also apply to other flavonoid genes, particularly in the case of CHI. There is also a growing awareness that the ''promiscuity'' of metabolic enzymes such as ANS, as well as flavonoid glycosyltransferases (Lim et al, 2004) and O-methyltransferases (Deavours et al, 2006), is more the rule than the exception (Taglieber et al, 2007). These ''alternative'' functions of otherwise well-characterized proteins may represent new paradigms that must be taken into account in efforts to develop framework models of cellular metabolism.…”

Section: Discussionmentioning

confidence: 99%

Functional Analysis of a Predicted Flavonol Synthase Gene Family in Arabidopsis

et al. 2008

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The genome of Arabidopsis (Arabidopsis thaliana) contains five sequences with high similarity to FLAVONOL SYNTHASE1 (AtFLS1), a previously characterized flavonol synthase gene that plays a central role in flavonoid metabolism. This apparent redundancy suggests the possibility that Arabidopsis uses multiple isoforms of FLS with different substrate specificities to mediate the production of the flavonols, quercetin and kaempferol, in a tissue-specific and inducible manner. However, biochemical and genetic analysis of the six AtFLS sequences indicates that, although several of the members are expressed, only AtFLS1 encodes a catalytically competent protein. AtFLS1 also appears to be the only member of this group that influences flavonoid levels and the root gravitropic response in seedlings under nonstressed conditions. This study showed that the other expressed AtFLS sequences have tissue- and cell type-specific promoter activities that overlap with those of AtFLS1 and encode proteins that interact with other flavonoid enzymes in yeast two-hybrid assays. Thus, it is possible that these “pseudogenes” have alternative, noncatalytic functions that have not yet been uncovered.

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Section: Discussionmentioning

confidence: 99%

Functional Analysis of a Predicted Flavonol Synthase Gene Family in Arabidopsis

et al. 2008

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“…An apparent value for the enantioselectivity (E app ) in the hydrolysis of 3-bromo-2-methylpropionate was estimated as ca. 41. It was further shown that 2-bromopropionate inhibited the esterase activity and that p-nitrophenyl butyrate inhibited the haloacid dehalogenase activity.…”

Section: ) Activitymentioning

confidence: 95%

“…perform catalysis at an alternative active site (enzyme alternate-site promiscuity). [40,41] The phenomenon of enzyme catalytic promiscuity in the field of biocatalysis has been highlighted in several review articles. [40,[42][43][44][45][46][47][48][49][50][51][52][53][54][55][56][57][58][59] …”

Section: Enzyme Promiscuity Different Types Of Enzyme Promiscuitymentioning

confidence: 99%

Biocatalytic Promiscuity

2011

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Enzymes are attractive catalysts because of their promiscuity and their ability to perform highly regio‐, chemo‐ and stereoselective transformations. Enzyme promiscuity allows optimisation of industrial processes that require reaction conditions different from those in nature. Many enzymes can be used in reactions completely different from the reaction the enzyme originally evolved to perform. Such catalytically promiscuous reactions can be secondary activities hidden behind a native activity and might be discovered either in screening for that particular activity or, alternatively, by chance. Recently, researchers have designed enzymes to show catalytic promiscuity. It is also possible to design new enzymes from scratch by computer modelling (de novo design), but most work published to date starts from a known enzyme backbone. Promiscuous activity might also be induced or enhanced by rational design or directed evolution (or combinations thereof). Enzyme catalytic promiscuity provides fundamental knowledge about enzyme/substrate interactions and the evolution of new enzymes. New enzymes are required by industry, which needs to optimise chemical processes in an environmentally sustainable way. In this review various aspects of enzyme catalytic promiscuity are considered from a biocatalytic perspective.

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“…It constitutes a very important property of many enzymes, having a natural role in evolution and, occasionally, in the biosynthesis of secondary metabolites. [1][2][3][4][5][6][7] For example, it has been demonstrated that vanadium-dependent chloroperoxidase shows phosphatase activity when vanadate is not present, indicating that its active site is very similar to that of the acid phosphatases. 8 On the other hand, it was found that an acid phosphatase from plants (in contrast to the kidney bean purple acid phosphatase (PAP)) uniquely exhibits chloroperoxidase activity with loss of phosphatase activity when orthovanadate is added to the apo form of the enzyme.…”

Section: Introductionmentioning

confidence: 99%

“…11,12 Nevertheless, no catecholase activity for any of the well characterized PAPs has as yet been described. While several enzymes displaying catalytic promiscuity have been the subject of recent related investigations, [1][2][3][4][5][6][7] there are few examples of synthetic analogues which exhibit such multifunctional activities. [13][14][15][16][17][18] In recent years, considerable attention has been devoted to the synthesis, X-ray structural analysis and physicochemical characterization of structural and functional dinuclear Fe III M II mimetics for the active site of metallohydrolases such as purple acid phosphatase.…”

Section: Introductionmentioning

confidence: 99%

Catalytic promiscuity: catecholase-like activity and hydrolytic DNA cleavage promoted by a mixed-valence FeIII FeII complex

Neves¹,

Bortoluzzi²,

Jovito³

et al. 2010

J. Braz. Chem. Soc.

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Os estudos sobre enzimas têm mostrado que existe uma relação clara entre a evolução enzimática e a propriedade de promiscuidade catalítica que elas podem apresentar. Com isto, o desenvolvimento de sistemas biomiméticos capazes de atuar de modo promíscuo, de forma similar a algumas enzimas, mostrou-se um novo desafio para os químicos bioinorgânicos. Neste trabalho, reportamos a estrutura de raios X e os estudos em solução e de promiscuidade catalítica do complexo [(bpbpmp)Fe . Assim, o complexo 1 apresenta atividades de hidrolase e oxidoredutase, sendo um interessante modelo sintético para estudos de promiscuidade catalítica.Catalytic promiscuity has emerged as an important property of many enzymes since the relationship of this property to enzymatic evolution became clear. Simultaneously, the development of suitable biomimetic catalytic systems capable of mimicking the promiscuous catalytic properties of such enzymes represents a new challenge for bioinorganic chemists. In this paper we report on the X-ray structure, the solution studies and the promiscuous catalytic activity of the mixed-valence complex [(bpbpmp)Fe III (m-OAc) 2 Fe II ](ClO 4 ), (1), containing the unsymmetrical dinucleating ligand 2-{[(2-hydroxybenzyl)(2-pyridylmethyl)aminomethyl]-4-methyl-6-[bis(2-pyridylmethyl) aminomethyl]}phenol (H 2 bpbpmp). Potentiometric and spectrophotometric titrations and kinetics studies showed that this coordination compound generates active species that promote hydrolytic cleavage of double strand DNA (dsDNA), with a rate enhancement of 1.9×10 8 over the non-catalyzed reaction, as well as promote oxidation of 3,5-di-tert-butylcatechol (3,5-dtbc), with k cat = 1.16 × 10 -2 s -1and K M = 7.1×10 -4 mol L -1. Thus, complex 1 shows both hydrolase and oxidoreductase activities and can be regarded as a man-made model for studying catalytic promiscuity.

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Alternate‐Site Enzyme Promiscuity

Abstract: Promiscuous reactions get around: It is shown that promiscuous enzyme‐catalyzed reactions (i.e., the catalysis of distinctly different chemical transformations) can also take place at sites other than where the natural reaction occurs.

Cited by 58 publications

References 48 publications

Functional Analysis of a Predicted Flavonol Synthase Gene Family in Arabidopsis

Functional Analysis of a Predicted Flavonol Synthase Gene Family in Arabidopsis

Biocatalytic Promiscuity

Catalytic promiscuity: catecholase-like activity and hydrolytic DNA cleavage promoted by a mixed-valence FeIII FeII complex

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