Efficient Catalytic Promiscuity for Chemically Distinct Reactions

Babtie, Ann C.; Bandyopadhyay, Subhajit; Olguín, Luis F.; Hollfelder, Florian

doi:10.1002/anie.200805843

Cited by 57 publications

(85 citation statements)

References 32 publications

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“…The x-ray structure of BcPMH confirms that it is structurally and mechanistically closely related to arylsulfatases and also, albeit more distantly, to AP and nucleotide phosphodiesterase (11,13). These three enzymes catalyze at least two reactions besides their native activity that are the native reactions of another family member (14)(15)(16)(17)(18)(19). BcPMH promotes all native reactions of these three enzymes, making catalytic promiscuity a widespread feature of this superfamily.…”

Section: Discussionmentioning

confidence: 63%

“…PMH is a member of the alkaline phosphatase (AP) superfamily that encompasses structurally related enzymes known to hydrolyze phosphate monoesters and diesters and sulfate monoesters (13). Several members of the AP superfamily show catalytic promiscuity, and in some cases the promiscuous reactions are the native activities of other superfamily members (14)(15)(16)(17)(18)(19).BcPMH catalyzes the hydrolysis of a total of six different substrate classes, four of which correspond to activities seen in the AP superfamily. The collection of substrate classes, for which rate accelerations between 10 7 and 10 19 are observed, encompasses large variations in charge, the reaction center, size, hydrophobicity, reactivity, and nature of the TS of the uncatalyzed reaction.…”

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confidence: 99%

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confidence: 99%

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An efficient, multiply promiscuous hydrolase in the alkaline phosphatase superfamily

Loo

Jonas

Babtie

et al. 2010

Proc. Natl. Acad. Sci. U.S.A.

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164

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We report a catalytically promiscuous enzyme able to efficiently promote the hydrolysis of six different substrate classes. Originally assigned as a phosphonate monoester hydrolase (PMH) this enzyme exhibits substantial second-order rate accelerations (ðk cat ∕K M Þ∕ k w ), ranging from 10 7 to as high as 10 19 , for the hydrolyses of phosphate mono-, di-, and triesters, phosphonate monoesters, sulfate monoesters, and sulfonate monoesters. This substrate collection encompasses a range of substrate charges between 0 and −2, transition states of a different nature, and involves attack at two different reaction centers (P and S). Intrinsic reactivities (half-lives) range from 200 days to 10 5 years under near neutrality. The substantial rate accelerations for a set of relatively difficult reactions suggest that efficient catalysis is not necessarily limited to efficient stabilization of just one transition state. The crystal structure of PMH identifies it as a member of the alkaline phosphatase superfamily. PMH encompasses four of the native activities previously observed in this superfamily and extends its repertoire by two further activities, one of which, sulfonate monoesterase, has not been observed previously for a natural enzyme. PMH is thus one of the most promiscuous hydrolases described to date. The functional links between superfamily activities can be presumed to have played a role in functional evolution by gene duplication.catalytic promiscuity | evolution | mechanism | sulfatase | superfamily E nzymes are usually seen as highly specific catalysts following the classical rule "one enzyme, one activity." This view is challenged by an increasing number of enzymes with broad substrate specificities or side activities indicating that enzymes are catalytically more flexible than originally assumed. Some of these promiscuous enzymes can turn over substrates with different structures while catalyzing the same chemical reaction involving the same transition state (substrate promiscuity). Catalytic promiscuity, by contrast, is the ability of an enzyme to catalyze chemically distinct reactions by stabilization of different transition states (TSs) (1). Catalytic efficiencies (k cat ∕K M ) for the promiscuous substrates are often substantially lower (2 to 9 orders of magnitude) than for the native conversions (1-3). The growing number of examples of this phenomenon (1-4) has engendered excitement on a number of fronts. Catalytic promiscuity provides a functional basis for enzyme evolution by gene duplication. The initial head-start activity of the duplicated gene copy could support an immediate selective advantage (1, 2, 5, 6), to be followed by improvement of the initially weak activity (7). Even low k cat ∕K M values for a promiscuous function can support a significant selective advantage (8). Mimicking this evolutionary shortcut could also provide a more efficient route to changing the function of proteins by directed evolution (5).We describe multiple and efficient catalytic promiscuity in an enzyme from Burkh...

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Section: Discussionmentioning

confidence: 63%

mentioning

confidence: 99%

mentioning

confidence: 99%

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An efficient, multiply promiscuous hydrolase in the alkaline phosphatase superfamily

Loo

Jonas

Babtie

et al. 2010

Proc. Natl. Acad. Sci. U.S.A.

Self Cite

164

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“…Although it is well known that a given enzyme is able to catalyze a specific reaction efficiently, some unexpected experimental results have indicated that many enzymes are catalytically promiscuous; i.e., they have the ability to catalyze distinctly different reactions (Copley, 2003;Khersonsky et al, 2006;Hult and Berglund, 2007). Many instances of this phenomenon have recently been reported (Babtie et al, 2009;Hasnaoui-Dijoux et al, 2008;Lou et al, 2008;Olguin et al, 2008;Sharma et al, 2009;Svedendahl et al, 2008;Taglieber et al, 2007;Xu et al, 2007).…”

Section: Introductionmentioning

confidence: 94%

Promiscuous protease-catalyzed aldol reactions: A facile biocatalytic protocol for carbon–carbon bond formation in aqueous media

Zhou

Wang

et al. 2010

Journal of Biotechnology

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“…In contrast, catalytic promiscuous enzymes carry out a secondary reaction that results in a chemical transformation different from that catalyzed with its canonical substrate [11]. In this context, catalytic promiscuity may become less efficient than the primary reaction, such as the secondary phosphoserine phosphatase activity of HisB (UniProt:P06987) and , whereas the secondary reaction of hydrolysis of bis(4-nitrophenyl) phosphate has a k cat /K M of 2.5 × 10 5 M −1 s −1 [16]. These examples show that the rate constant for many promiscuous reactions are within the range of physiologically relevant reactions, which k cat /K M round between 10 3 and 10 5 M −1 s −1 as observed in metabolic enzymes [11].…”

Section: How Many Kinds Of Promiscuity Are There?mentioning

confidence: 99%

Do lifestyles influence the presence of promiscuous enzymes in bacteria and Archaea metabolism?

Martínez-Núñez

Pérez‐Rueda

2016

Sustain Chem Process

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The adequacy of an organism to the environment depends in part on its ability to modify its repertoire of cellular components, such as transporters, regulatory proteins and metabolic enzymes. In this review we discuss some recent results showing how the environment influences the content of promiscuous enzymes in bacterial and archaeal metabolism. In this regard, the proportion of promiscuous enzymes do not depend on genome size, as has been reported for the complete repertoire of enzymes, but it is influenced by the lifestyles, where the fraction of promiscuous enzymes is high in free-living organisms, while there is a small fraction in intracellular organisms. Therefore, promiscuous enzymes are enriched in organisms that inhabit fluctuating environments, providing bacteria with an enzymatic repertoire of new activities that helps to face multiple ecological variables. Finally, we discuss the possible role of gene duplications that occur most frequently in promiscuous enzymes of free-living organisms, which aid expand the universe of possible functions.

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Efficient Catalytic Promiscuity for Chemically Distinct Reactions

Cited by 57 publications

References 32 publications

An efficient, multiply promiscuous hydrolase in the alkaline phosphatase superfamily

An efficient, multiply promiscuous hydrolase in the alkaline phosphatase superfamily

Promiscuous protease-catalyzed aldol reactions: A facile biocatalytic protocol for carbon–carbon bond formation in aqueous media

Do lifestyles influence the presence of promiscuous enzymes in bacteria and Archaea metabolism?

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