ArticleeLife2015
Extensive site-directed mutagenesis reveals interconnected functional units in the alkaline phosphatase active site.
Article in eLife, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 34 papers, 1 of them a synthesis that pooled it.
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Who cites it
34 citing papers in PubMed, 1 synthesis or guideline pooled it.
- Potential Bioactive Function of Microbial Metabolites as Inhibitors of Tyrosinase: A Systematic Review.International journal of molecular sciences · 2026Pooled it
- One-site polarity switch enhances catalytic efficiency and stability of D-allulose 3-epimerase via flexibility-rigidity rebalancing.Scientific reports · 2026Article
- Free energy perturbations in enzyme kinetic models reveal cryptic epistasis.PLoS computational biology · 2026Article
- Using residue interaction networks to understand protein function and evolution and to engineer new proteins.Current opinion in structural biology · 2024Review
- Pervasive epistasis exposes intramolecular networks in adaptive enzyme evolution.Nature communications · 2023Article
- Domain acquisition by class I aminoacyl-tRNA synthetase urzymes coordinated the catalytic functions of HVGH and KMSKS motifs.Nucleic acids research · 2023Article
- Second-Shell Residues Contribute to Catalysis by Predominately Preorganizing the Apo State in PafA.Journal of the American Chemical Society · 2023Article
- Non-active Site Residue in Loop L4 Alters Substrate Capture and Product Release in d-Arginine Dehydrogenase.Biochemistry · 2023Article
- Genetic Perturbation Alters Functional Substates in Alkaline Phosphatase.Journal of the American Chemical Society · 2023Article
- High-Throughput Steady-State Enzyme Kinetics Measured in a Parallel Droplet Generation and Absorbance Detection Platform.Analytical chemistry · 2022Article
- Essential Functional Interplay of the Catalytic Groups in Acid Phosphatase.ACS catalysis · 2022Article
- High throughput and quantitative enzymology in the genomic era.Current opinion in structural biology · 2021Review
- Revealing enzyme functional architecture via high-throughput microfluidic enzyme kinetics.Science (New York, N.Y.) · 2021Article
- The high catalytic rate of the cold-active Vibrio alkaline phosphatase requires a hydrogen bonding network involving a large interface loop.FEBS open bio · 2021Article
- Article
- Higher-order epistasis shapes the fitness landscape of a xenobiotic-degrading enzyme.Nature chemical biology · 2019Article
- Accurate high-throughput screening based on digital protein synthesis in a massively parallel femtoliter droplet array.Science advances · 2019Article
- Evolutionary repurposing of a sulfatase: A new Michaelis complex leads to efficient transition state charge offset.Proceedings of the National Academy of Sciences of the United States of America · 2018Article
- Darwin Assembly: fast, efficient, multi-site bespoke mutagenesis.Nucleic acids research · 2018Article
- Article
Corrections and comments
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Authors and funding
5 authors.
Funding
Abstract
Enzymes enable life by accelerating reaction rates to biological timescales. Conventional studies have focused on identifying the residues that have a direct involvement in an enzymatic reaction, but these so-called 'catalytic residues' are embedded in extensive interaction networks. Although fundamental to our understanding of enzyme function, evolution, and engineering, the properties of these networks have yet to be quantitatively and systematically explored. We dissected an interaction network of five residues in the active site of Escherichia coli alkaline phosphatase. Analysis of the complex catalytic interdependence of specific residues identified three energetically independent but structurally interconnected functional units with distinct modes of cooperativity. From an evolutionary perspective, this network is orders of magnitude more probable to arise than a fully cooperative network. From a functional perspective, new catalytic insights emerge. Further, such comprehensive energetic characterization will be necessary to benchmark the algorithms required to rationally engineer highly efficient enzymes.
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Registered trials
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.