Affinage

DERA

Deoxyribose-phosphate aldolase · UniProt Q9Y315

Length
318 aa
Mass
35.2 kDa
Annotated
2026-06-09
22 papers in source corpus 6 papers cited in narrative 6 extracted findings
Cross-family judge vs UniProt: Affinage preferred faithfulness: 4/4 claims corpus-supported (100%)

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

DERA encodes a class I aldolase that catalyzes the reversible retro-aldol cleavage of 2-deoxy-D-ribose-5-phosphate into glyceraldehyde-3-phosphate and acetaldehyde, operating through a Schiff base intermediate at an active-site lysine (PMID:6749498, PMID:25229427). Catalysis depends on an intrinsically disordered C-terminal tail that samples a catalytically competent closed conformation in which the terminal tyrosine Y259 enters the active site to drive the proton-abstraction step, with auxiliary phosphate-binding residues orienting Y259 (PMID:30101036); a non-canonical phosphate-binding site (Ser238/Ser239) further tunes catalytic efficiency by coupling protein-wide anticorrelated motions to the transition state (PMID:29910900). Substrate donor preference is governed by active-site and proximal residues, and the enzyme can also accept formaldehyde as a donor, while crotonaldehyde formed from acetaldehyde self-condensation irreversibly inactivates the enzyme via a covalent Michael adduct with Cys47 (PMID:28347769, PMID:33147349). Beyond its catalytic role, human DERA links deoxynucleoside catabolism to cellular stress responses: it enables ATP production from extracellular deoxyinosine, interacts with the stress granule component YBX1, and is recruited to stress granules under oxidative or mitochondrial stress, where its loss reduces stress granule formation and increases apoptosis (PMID:25229427).

Mechanistic history

Synthesis pass · year-by-year structured walk · 6 steps
  1. 1982 Medium

    Establishing that the deoC gene product is a class I aldolase resolved how 2-deoxyribose-5-phosphate is cleaved, identifying a Schiff base mechanism centered on an active-site lysine.

    Evidence DNA/protein sequencing, amino acid composition, and catalytic characterization of E. coli deoxyriboaldolase

    PMID:6749498

    Open questions at the time
    • Active-site lysine was only tentatively assigned
    • No structural model of the catalytic site
    • Human ortholog not yet addressed
  2. 2014 High

    Characterizing human DERA extended the enzyme's role beyond metabolism, showing it both supports deoxynucleoside-derived ATP production and participates in stress granule biology via YBX1, linking a metabolic enzyme to cell survival under stress.

    Evidence Enzymatic assays, DERA–YBX1 co-immunoprecipitation, shRNA knockdown with stress granule imaging and apoptosis readouts, and deoxyinosine ATP-rescue experiments in human cells

    PMID:25229427

    Open questions at the time
    • Mechanism of DERA recruitment to stress granules unknown
    • Whether YBX1 interaction is direct or scaffold-mediated not resolved
    • Catalytic activity not shown to be required for the stress granule function
  3. 2015 High

    Identifying a non-canonical Ser238/Ser239 phosphate-binding site and linking transition-state thermodynamics to protein-wide anticorrelated motions explained how distributed dynamics contribute to catalytic efficiency.

    Evidence Site-directed/saturation mutagenesis, kinetic and thermodynamic analysis, and MD simulations of E. coli DERA

    PMID:29910900

    Open questions at the time
    • Physical basis coupling distal motions to active-site chemistry not fully defined
    • Relevance of these dynamics to the human enzyme untested
  4. 2017 Medium

    Defining the covalent Cys47–crotonaldehyde adduct explained the long-observed irreversible inactivation of DERA by acetaldehyde, and the C47L variant demonstrated this site can be engineered away.

    Evidence Site-directed mutagenesis, activity assays with acetaldehyde, and covalent adduct identification

    PMID:28347769

    Open questions at the time
    • Adduct structure characterized in a single lab
    • Whether Cys47 inactivation occurs in human cells not tested
  5. 2018 High

    Solving the closed-state conformation of the disordered C-terminal tail established Y259 as a mobile catalytic residue that completes the active site for proton abstraction, defining a conformational gating mechanism.

    Evidence NMR solution-structure determination, H/D exchange, phosphate titration, and MD simulations of E. coli DERA

    PMID:30101036

    Open questions at the time
    • Kinetics of open/closed interconversion under turnover not quantified
    • Tail dynamics in human DERA not examined
  6. 2020 Medium

    Mapping the 24 active-site and proximal residues that control donor preference defined the determinants of substrate specificity and showed the enzyme can use C1/C2 donors, informing both mechanism and engineering.

    Evidence Structure-guided and machine-learning-guided mutagenesis with multi-substrate activity assays in E. coli DERA

    PMID:33147349

    Open questions at the time
    • Specificity determinants validated in the bacterial enzyme only
    • Structural basis of altered donor binding not directly resolved

Open questions

Synthesis pass · forward-looking unresolved questions
  • Whether DERA's catalytic activity is mechanistically required for its stress granule recruitment and pro-survival function in human cells remains unresolved.
  • No catalytically dead human DERA mutant tested in the stress granule context
  • Physiological source and flux of deoxyinosine substrate in vivo undefined
  • Structural model of human DERA C-terminal tail/Y259 not reported

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0016829 lyase activity 5 GO:0016740 transferase activity 3
Localization
GO:0005829 cytosol 1
Pathway
R-HSA-1430728 Metabolism 1 R-HSA-8953897 Cellular responses to stimuli 1
Partners
YBX1

Evidence

Reading pass · 6 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
1982 E. coli deoC gene encodes 2-deoxyribose-5-phosphate aldolase (deoxyriboaldolase), a 259-amino acid class I aldolase (MW 27,737) that forms Schiff base intermediates during catalysis; a lysine residue was tentatively identified as the active-site residue involved in Schiff base formation. DNA/protein sequencing, amino acid composition analysis, catalytic property characterization European journal of biochemistry Medium 6749498
2014 Human DERA is the deoxyribose-phosphate aldolase responsible for converting 2-deoxy-D-ribose-5-phosphate into glyceraldehyde-3-phosphate and acetaldehyde; DERA interacts with stress granule component YBX1 and is recruited to stress granules upon oxidative or mitochondrial stress; shRNA-mediated knockdown of DERA reduced stress granule formation and increased apoptosis after clotrimazole stress; DERA activity enables cells with abolished mitochondrial ATP production to use extracellular deoxyinosine to maintain ATP levels via deoxynucleoside degradation. Enzymatic activity assays, co-immunoprecipitation (DERA–YBX1), shRNA knockdown with stress granule imaging and apoptosis readouts, ATP rescue experiments Biochimica et biophysica acta High 25229427
2018 The C-terminal tail of E. coli DERA is intrinsically disordered and samples open and catalytically relevant closed conformations; in the closed state, the terminal tyrosine residue Y259 enters the active site and is required for the proton abstraction step of catalysis; auxiliary phosphate-binding residues on the C-terminal tail help orient Y259 for catalysis. NMR spectroscopy (NOE distance restraints, H/D exchange, phosphate titration), molecular dynamics simulations, solution-state structure determination of closed state ACS catalysis High 30101036
2015 A non-canonical phosphate-binding site in DERA, consisting of Ser238 and Ser239, contributes to catalytic efficiency; the S239P mutant showed increased enthalpy but reduced entropy at the transition state, with a concomitant loss in anticorrelated protein motions distributed across the enzyme; the degree of anticorrelated (protein-wide) motions is coupled to catalytic efficiency in the DERA retro-aldol reaction. Site-directed and site-saturation mutagenesis, kinetic analysis of mutants, molecular dynamics simulations, temperature-dependence of catalytic rates Chemical science High 29910900
2017 Cysteine 47 (C47) in DERA forms a covalent Michael adduct with crotonaldehyde (a side-product of acetaldehyde self-condensation), constituting the primary mechanism of irreversible inhibition of DERA by acetaldehyde; the C47L substitution abolishes this inhibition while preserving stereoselectivity. Site-directed mutagenesis, activity assays with acetaldehyde, identification of covalent inhibitor-adduct Journal of biotechnology Medium 28347769
2020 E. coli DERA active-site and proximal residues at 24 positions govern substrate donor preference; targeted mutagenesis of these residues improved acetaldehyde (C2) donor activity 2–3-fold while abolishing activity toward the natural donor glyceraldehyde-3-phosphate; wild-type DERA can also use formaldehyde (C1) as donor substrate. Structure-guided site-directed mutagenesis (1–3 mutations), enzyme activity assays with multiple substrates, machine-learning-guided mutagenesis rounds Applied microbiology and biotechnology Medium 33147349

Source papers

Stage 0 corpus · 22 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
1982 The primary structure of Escherichia coli K12 2-deoxyribose 5-phosphate aldolase. Nucleotide sequence of the deoC gene and the amino acid sequence of the enzyme. European journal of biochemistry 45 6749498
1984 Structure and function of the intercistronic regulatory deoC-deoA element of Escherichia coli K-12. The EMBO journal 33 6323164
2018 2-Deoxy-D-ribose-5-phosphate aldolase (DERA): applications and modifications. Applied microbiology and biotechnology 29 30284013
2014 DERA is the human deoxyribose phosphate aldolase and is involved in stress response. Biochimica et biophysica acta 25 25229427
2020 Substrate specificity of 2-deoxy-D-ribose 5-phosphate aldolase (DERA) assessed by different protein engineering and machine learning methods. Applied microbiology and biotechnology 19 33147349
2013 A highly productive, whole-cell DERA chemoenzymatic process for production of key lactonized side-chain intermediates in statin synthesis. PloS one 17 23667462
2018 Conformational Sampling of the Intrinsically Disordered C-Terminal Tail of DERA Is Important for Enzyme Catalysis. ACS catalysis 13 30101036
2017 Probing the acetaldehyde-sensitivity of 2-deoxy-ribose-5-phosphate aldolase (DERA) leads to resistant variants. Journal of biotechnology 11 28347769
2019 Seed morphology using SEM techniques for identification of useful grasses in Dera Ghazi Khan, Pakistan. Microscopy research and technique 10 31738478
2010 The fed-batch production of a thermophilic 2-deoxyribose-5-phosphate aldolase (DERA) in Escherichia coli by exponential feeding strategy control. Applied biochemistry and biotechnology 10 20229283
2015 Linking coupled motions and entropic effects to the catalytic activity of 2-deoxyribose-5-phosphate aldolase (DERA). Chemical science 9 29910900
2016 A report on the molecular detection and seasonal prevalence of Trypanosoma brucei in Dromedary Camels from Dera Ghazi Khan District in Southern Punjab (Pakistan). Tropical biomedicine 6 33579093
2020 Genetic variants in TKT and DERA in the nicotinamide adenine dinucleotide phosphate pathway predict melanoma survival. European journal of cancer (Oxford, England : 1990) 5 32659474
2003 Mutations in deoB and deoC alter an extracellular signaling pathway required for activation of the gab operon in Escherichia coli. FEMS microbiology letters 4 14612251
2023 Genomic selection pressure discovery using site-frequency spectrum and reduced local variability statistics in Pakistani Dera-Din-Panah goat. Tropical animal health and production 3 37750990
2020 Haematological outcomes in progression of malaria: A cohort study from district Dera Ismail Khan, Pakistan. JPMA. The Journal of the Pakistan Medical Association 3 33159762
2007 Establishment and characterization of a cell line (DEOC-1) originating from a human malignant melanoma of the skin. Human cell 3 17547717
2023 Genetic basis of ß-thalassemia in families of pashtun ethnicity in Dera Ismail Khan district of Khyber Pakhtun-Khwa province, Pakistan. Expert review of hematology 1 37491848
2014 Characterization of the etiological agents of tuberculous lymphadenitis in Dera Woreda, North Showa, Ethiopia. Ethiopian medical journal 1 24696983
2026 Role of the Mycoplasma bovis deoC gene in nucleoside catabolism and host cell survival. Applied and environmental microbiology 0 42117702
2025 Flow Synthesis of Pharmaceutical Intermediate Catalyzed by Immobilized DERA: Comparison of Different Immobilization Techniques and Reactor Designs. Molecules (Basel, Switzerland) 0 40509167
2025 Epidemiological Study of Dengue Fever in a Tertiary Care Hospital in Dera Ismail Khan, Pakistan. Cureus 0 40895961

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