ArticleJournal of molecular biology2008
A study in molecular contingency: glutamine phosphoribosylpyrophosphate amidotransferase is a promiscuous and evolvable phosphoribosylanthranilate isomerase.
Article in Journal of molecular biology, 2008. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 27 papers.
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Who cites it
27 citing papers in PubMed.
- Dan Tawfik's Lessons for Protein Engineers about Enzymes Adapting to New Substrates.Biochemistry · 2023Review
- Structure and kinetics of indole-3-glycerol phosphate synthase fromThe Journal of biological chemistry · 2020Article
- Structural and functional innovations in the real-time evolution of new (βα)Proceedings of the National Academy of Sciences of the United States of America · 2017Article
- Mechanistic and Evolutionary Insights from the Reciprocal Promiscuity of Two Pyridoxal Phosphate-dependent Enzymes.The Journal of biological chemistry · 2016Article
- Co-occurrence of analogous enzymes determines evolution of a novel (βα)8-isomerase sub-family after non-conserved mutations in flexible loop.The Biochemical journal · 2016Article
- Long-Term Persistence of Bi-functionality Contributes to the Robustness of Microbial Life through Exaptation.PLoS genetics · 2016Article
- The Impact of Non-Enzymatic Reactions and Enzyme Promiscuity on Cellular Metabolism during (Oxidative) Stress Conditions.Biomolecules · 2015Review
- Rapid bursts and slow declines: on the possible evolutionary trajectories of enzymes.Journal of the Royal Society, Interface · 2015Review
- An alternate pathway of arsenate resistance in E. coli mediated by the glutathione S-transferase GstB.ACS chemical biology · 2015Article
- Promiscuous and adaptable enzymes fill "holes" in the tetrahydrofolate pathway in Chlamydia species.mBio · 2014Article
- Copy-number changes in evolution: rates, fitness effects and adaptive significance.Frontiers in genetics · 2013Review
- Early evolution of efficient enzymes and genome organization.Biology direct · 2012Article
- Characterization of the indole-3-glycerol phosphate synthase from Pseudomonas aeruginosa PAO1.The protein journal · 2012Article
- The Streptomyces-produced antibiotic fosfomycin is a promiscuous substrate for archaeal isopentenyl phosphate kinase.Biochemistry · 2012Article
- Toward a systems biology perspective on enzyme evolution.The Journal of biological chemistry · 2012Review
- Computer-Aided Protein Directed Evolution: a Review of Web Servers, Databases and other Computational Tools for Protein Engineering.Computational and structural biotechnology journal · 2012Review
- Purine biosynthesis in archaea: variations on a theme.Biology direct · 2011Article
- Assessing directed evolution methods for the generation of biosynthetic enzymes with potential in drug biosynthesis.Future medicinal chemistry · 2011Article
- Artificial gene amplification reveals an abundance of promiscuous resistance determinants in Escherichia coli.Proceedings of the National Academy of Sciences of the United States of America · 2011Article
- De novo designed proteins from a library of artificial sequences function in Escherichia coli and enable cell growth.PloS one · 2011Article
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2 authors.
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Abstract
The prevalence of paralogous enzymes implies that novel catalytic functions can evolve on preexisting protein scaffolds. The weak secondary activities of proteins, which reflect catalytic promiscuity and substrate ambiguity, are plausible starting points for this evolutionary process. In this study, we observed the emergence of a new enzyme from the ASKA (A Complete Set of E. coli K-12 ORF Archive) collection of Escherichia coli open reading frames. The overexpression of (His)(6)-tagged glutamine phosphoribosylpyrophosphate amidotransferase (PurF) unexpectedly rescued a Delta trpF E. coli strain from starvation on minimal media. The wild-type PurF and TrpF enzymes are unrelated in sequence, tertiary structure and catalytic mechanism. The promiscuous phosphoribosylanthranilate isomerase activity of the ASKA PurF variant apparently stems from a preexisting affinity for phosphoribosylated substrates. The relative fitness of the (His)(6)-PurF/Delta trpF strain was improved 4.8-fold to nearly wild-type levels by random mutagenesis of purF and genetic selection. The evolved and ancestral PurF proteins were purified and reacted with phosphoribosylanthranilate in vitro. The best evolvant (k(cat)/K(M)=0.3 s(-1) M(-1)) was approximately 25-fold more efficient than its ancestor but >10(7)-fold less efficient than the wild-type phosphoribosylanthranilate isomerase. These observations demonstrate in quantitative terms that the weak secondary activities of promiscuous enzymes can dramatically improve the fitness of contemporary organisms.
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