Moonlighting enzymes: when cellular context defines specificity

Gupta, Munishwar N.; Uversky, Vladimir N.

doi:10.1007/s00018-023-04781-0

Cited by 27 publications

(14 citation statements)

References 261 publications

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“…Here, the binding site/active site can be same or even different, proving that the contention by Ringe (1995) was correct. Moonlighting is closer to the catalytic promiscuity in the sense that very different kinds of biological activities are exhibited by very similar kinds of protein molecules (Gupta & Uversky, 2023d, 2023e, 2023f).…”

Section: Preformed Binding Site and Inducible Formation Of Binding Sitesmentioning

confidence: 99%

Protein structure–function continuum model: Emerging nexuses between specificity, evolution, and structure

Gupta,

Uversky

2024

Protein Science

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The rationale for replacing the old binary of structure–function with the trinity of structure, disorder, and function has gained considerable ground in recent years. A continuum model based on the expanded form of the existing paradigm can now subsume importance of both conformational flexibility and intrinsic disorder in protein function. The disorder is actually critical for understanding the protein–protein interactions in many regulatory processes, formation of membrane‐less organelles, and our revised notions of specificity as amply illustrated by moonlighting proteins. While its importance in formation of amyloids and function of prions is often discussed, the roles of intrinsic disorder in infectious diseases and protein function under extreme conditions are also becoming clear. This review is an attempt to discuss how our current understanding of protein function, specificity, and evolution fit better with the continuum model. This integration of structure and disorder under a single model may bring greater clarity in our continuing quest for understanding proteins and molecular mechanisms of their functionality.

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Section: Preformed Binding Site and Inducible Formation Of Binding Sitesmentioning

confidence: 99%

Protein structure–function continuum model: Emerging nexuses between specificity, evolution, and structure

Gupta,

Uversky

2024

Protein Science

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“…These unusual applications mostly become possible because of what is called enzyme promiscuity. 26,[83][84][85][86][87][88][89][90] Substrate promiscuity refers to what has been known as the broad specicity of enzymes. A lipase may hydrolyse fats and oils made up of different fatty acids.…”

Section: Promiscuity Enables Repurposing Of Enzymesmentioning

confidence: 99%

“…It refers to the catalysis of a reaction by an enzyme which is otherwise normally catalysed by an enzyme from another class among the six classes under EC classication. 90,95,96 An important example of catalytic promiscuity is catalysis of C-C bond formation in aqueous media, aqueousorganic cosolvent mixtures and low water containing nonaqueous media. So much of organic synthesis involves C-C bond formation.…”

Section: Promiscuity Enables Repurposing Of Enzymesmentioning

confidence: 99%

“…We have over-focussed on enzyme specicity even though so much has been possible in biotechnology because of non-specicity. 26,[83][84][85][86][87][88][89][90][91][92]97,98 With a change in mindset, more innovations would be possible. A good example of this is the use of inexpensive hydrolases such as amylase in bioremediation of alkanes.…”

Section: Summary and Future Possibilitiesmentioning

confidence: 99%

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White & grey biotechnologies for shaping a sustainable future

Roy¹,

Gupta²

2023

RSC Sustain.

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“…Among these sub-strategies, protein promiscuity stood out as a particularly potent mechanism for achieving multi-tasking. This encompassed various forms of promiscuity, such as substrate promiscuity, catalytic promiscuity, and promiscuous protein-protein interactions, all of which played a crucial role in expanding the functional repertoire of proteins [16]. Moonlighting proteins exhibit the remarkable ability to carry out multiple distinct functions autonomously, often without segregating these functions into separate domains within the protein structure [12].…”

Section: Introductionmentioning

confidence: 99%

The Distal-Proximal Relationships Among the Human Moonlighting Proteins: Evolutionary hotspots and Darwinian checkpoints

Nawn,

Hassan,

Sil

et al. 2023

Preprint

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Moonlighting proteins, known for their ability to perform multiple, often unrelated functions within a single polypeptide chain, challenge the traditional "one gene, one protein, one function" paradigm. As organisms evolved, their genomes remained relatively stable in size, but the introduction of post-translational modifications and sub-strategies like protein promiscuity and intrinsic disorder enabled multifunctionality. Enzymes, in particular, exemplify this phenomenon, engaging in unrelated processes alongside their primary catalytic roles. This study employs a systematic, quantitative informatics approach to shed light on human moonlighting protein sequences. Phylogenetic analyses of human moonlighting proteins are presented, elucidating the distal-proximal relationships among these proteins based on sequence-derived quantitative features. The findings unveil the captivating world of human moonlighting proteins, urging further investigations in the emerging field of moonlighting proteomics, with the potential for significant contributions to our understanding of multifunctional proteins and their roles in diverse cellular processes and diseases.

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Moonlighting enzymes: when cellular context defines specificity

Cited by 27 publications

References 261 publications

Protein structure–function continuum model: Emerging nexuses between specificity, evolution, and structure

Protein structure–function continuum model: Emerging nexuses between specificity, evolution, and structure

White & grey biotechnologies for shaping a sustainable future

The Distal-Proximal Relationships Among the Human Moonlighting Proteins: Evolutionary hotspots and Darwinian checkpoints

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