Evidence map›Paper›PMID 11714928›Full record

ArticleProtein science : a publication of the Protein Society2001

Catalytic and binding poly-reactivities shared by two unrelated proteins: The potential role of promiscuity in enzyme evolution.

L C James, D S Tawfik

Abstract read
In one paragraph

Article in Protein science : a publication of the Protein Society, 2001. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 21 papers.

0numbers the graph read from it
0cells of the map it votes in
21citing papers in PubMed
–field-weighted citation impact
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

21 citing papers in PubMed.

  1. Review
  2. Review
  3. Article
  4. Article
  5. Article
  6. Computational strategies for the design of new enzymatic functions.Archives of biochemistry and biophysics · 2015
    Review
  7. Are molecular alphabets universal enabling factors for the evolution of complex life?Origins of life and evolution of the biosphere : the journal of the International Society for the Study of the Origin of Life · 2013
    Article
  8. Article
  9. Extending biochemical databases by metabolomic surveys.The Journal of biological chemistry · 2011
    Review
  10. Article
  11. Review
  12. Article
  13. TRIM21 is an IgG receptor that is structurally, thermodynamically, and kinetically conserved.Proceedings of the National Academy of Sciences of the United States of America · 2008
    Article
  14. Article
  15. Article
  16. Article
  17. Article
  18. Control of stereoselectivity in an enzymatic reaction by backdoor access.Angewandte Chemie (International ed. in English) · 2006
    Article
  19. Article
  20. SiteLight: binding-site prediction using phage display libraries.Protein science : a publication of the Protein Society · 2003
    Article
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

2 authors.

L C JamesCentre for Protein Engineering, Cambridge CB2 2HQ, United Kingdom.
D S Tawfik

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

It is generally accepted that enzymes evolved via gene duplication of existing proteins. But duplicated genes can serve as a starting point for the evolution of a new function only if the protein they encode happens to exhibit some activity towards this new function. Although the importance of such catalytic promiscuity in enzyme evolution has been proposed, little is actually known regarding how common promiscuous catalytic activities are in proteins or their origins, magnitudes, and potential contribution to the survival of an organism. Here we describe a pattern of promiscuous activities in two completely unrelated proteins-serum albumins and a catalytic antibody (aldolase antibody 38C2). Despite considerable structural dissimilarities-in the shape of the cavities and the position of catalytic lysine residues-both active sites are able to catalyze the Kemp elimination, a model reaction for proton transfer from carbon. We also show that these different active sites can bind promiscuously an array of hydrophobic negatively charged ligands. We suggest that the basic active-site features of an apolar pocket and a lysine residue can act as a primitive active site allowing these promiscuous activities to take place. We also describe, by modelling product formation at different substrate concentrations, how promiscuous activities of this kind- inefficient and rudimentary as they are-can provide a considerable selective advantage and a starting point for the evolution of new functions.

Indexed as

CatalysisBinding SitesCatalytic DomainDose-Response Relationship, DrugEnzymesEvolution, MolecularHydrogen-Ion ConcentrationKineticsModels, ChemicalModels, MolecularProtein BindingProtein ConformationProteinsProtein Structure, SecondarySerum AlbuminTime FactorsEnzymesProteinsSerum Albumin

Identifiers

PMID11714928
PMCPMC2374036

What OpenQuestion holds

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Registered trials

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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.