ArticleJournal of the American Chemical Society2011
pK(a) coupling at the intein active site: implications for the coordination mechanism of protein splicing with a conserved aspartate.
Article in Journal of the American Chemical Society, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 24 papers.
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Who cites it
24 citing papers in PubMed.
- Regulation of N-terminal cleavage and splicing in mini-Ter DnaE-3 intein by E23G and R50Q mutations.Biotechnology letters · 2026Article
- A Genetically Encoded Homocysteine Precursor to Probe Protein Active Sites and to Addict Escherichia coli to a Noncanonical Amino Acid Directly Involved in Catalysis.Angewandte Chemie (International ed. in English) · 2025Article
- Extein residues regulate the catalytic function of Spl DnaX intein enzyme by restricting the near-attack conformations of the active-site residues.Protein science : a publication of the Protein Society · 2023Article
- Structural and biochemical analysis of a novel atypically split intein reveals a conserved histidine specific to cysteine-less inteins.Chemical science · 2023Article
- Nature-inspired protein ligation and its applications.Nature reviews. Chemistry · 2023Review
- SufB intein splicing in Mycobacterium tuberculosis is influenced by two remote conserved N-extein histidines.Bioscience reports · 2022Article
- Inteins in Science: Evolution to Application.Microorganisms · 2020Review
- Methods to Study the Structure and Catalytic Activity of cis-Splicing Inteins.Methods in molecular biology (Clifton, N.J.) · 2020Article
- Mycobacterial DnaB helicase intein as oxidative stress sensor.Nature communications · 2018Article
- An Atypical Mechanism of Split Intein Molecular Recognition and Folding.Journal of the American Chemical Society · 2018Article
- Exploring Intein Inhibition by Platinum Compounds as an Antimicrobial Strategy.The Journal of biological chemistry · 2016Article
- A Single Aspartate Coordinates Two Catalytic Steps in Hedgehog Autoprocessing.Journal of the American Chemical Society · 2016Article
- An Unprecedented Combination of Serine and Cysteine Nucleophiles in a Split Intein with an Atypical Split Site.The Journal of biological chemistry · 2015Article
- Backbone assignments of mini-RecA intein with short native exteins and an active N-terminal catalytic cysteine.Biomolecular NMR assignments · 2015Article
- SufB intein of Mycobacterium tuberculosis as a sensor for oxidative and nitrosative stresses.Proceedings of the National Academy of Sciences of the United States of America · 2015Article
- Dynamics differentiate between active and inactive inteins.European journal of medicinal chemistry · 2015Article
- ¹H, ¹³C and ¹⁵N NMR assignments of a Drosophila Hedgehog autoprocessing domain.Biomolecular NMR assignments · 2014Article
- Structural and dynamical features of inteins and implications on protein splicing.The Journal of biological chemistry · 2014Review
- Protein splicing: how inteins escape from precursor proteins.The Journal of biological chemistry · 2014Review
- Recent progress in intein research: from mechanism to directed evolution and applications.Cellular and molecular life sciences : CMLS · 2013Review
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5 authors.
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Abstract
Protein splicing is a robust multistep posttranslational process catalyzed by inteins. In the Mtu RecA intein, a conserved block-F aspartate (D422) coordinates different steps in protein splicing, but the precise mechanism is unclear. Solution NMR shows that D422 has a strikingly high pK(a) of 6.1, two units above the normal pK(a) of aspartate. The elevated pK(a) of D422 is coupled to the depressed pK(a) of another active-site residue, the block-A cysteine (C1). A C1A mutation lowers the D422 pK(a) to normal, while a D422G mutation increases the C1 pK(a) from 7.5 to 8.5. The pK(a) coupling and NMR structure determination demonstrate that protonated D422 serves as a hydrogen bond donor to stabilize the C1 thiolate and promote the N-S acyl shift, the first step of protein splicing. Additionally, in vivo splicing assays with mutations of D422 to Glu, Cys, and Ser show that the deprotonated aspartate is essential for splicing, most likely by deprotonating and activating the downstream nucleophile in transesterification, the second step of protein splicing. We propose that the sequential protonation and deprotonation of the D422 side chain is the coordination mechanism for the first two steps of protein splicing.
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