Jove
Visualize
Contact Us
JoVE
x logofacebook logolinkedin logoyoutube logo
ABOUT JoVE
OverviewLeadershipBlogJoVE Help Center
AUTHORS
Publishing ProcessEditorial BoardScope & PoliciesPeer ReviewFAQSubmit
LIBRARIANS
TestimonialsSubscriptionsAccessResourcesLibrary Advisory BoardFAQ
RESEARCH
JoVE JournalMethods CollectionsJoVE Encyclopedia of ExperimentsArchive
EDUCATION
JoVE CoreJoVE BusinessJoVE Science EducationJoVE Lab ManualFaculty Resource CenterFaculty Site
Terms & Conditions of Use
Privacy Policy
Policies

Related Experiment Videos

How well is enzyme function conserved as a function of pairwise sequence identity?

Weidong Tian1, Jeffrey Skolnick

  • 1Center of Excellence in Bioinformatics, University at Buffalo, The State University of New York, 901 Washington Street, Buffalo, NY 14203, USA.

Journal of Molecular Biology
|October 22, 2003
PubMed
Summary
This summary is machine-generated.

Related Concept Videos

You might also read

Related Articles

Articles linked to this work by shared authors, journal, and citation graph.

Sort by
Same author

Adversarial Sequence Mutations in AlphaFold and ESMFold Reveal Nonphysical Structural Invariance, Confidence Failures, and Concerns for Protein Design.

Computational and structural biotechnology journal·2026
Same author

Toward mechanistic virtual immune cells.

Nature biotechnology·2026
Same author

Understanding Substance Dependence: What Differentiates Addictive from Non-Addictive Drugs?

bioRxiv : the preprint server for biology·2026
Same author

A reliability-screened thalamocortical control-network phenotype tracks cocaine-use history in cocaine use disorder.

medRxiv : the preprint server for health sciences·2026
Same author

AlphaInterp: Mechanistic Interpretability of AlphaFold 3 Reveals How Evolutionary Information Shapes Protein Structure Prediction.

bioRxiv : the preprint server for biology·2026
Same author

PHENOCAUZ: Linking Human Symptoms, Drug Side Effects and Efficacy to Their Molecular Causes Using Mendelian Disease Biology.

bioRxiv : the preprint server for biology·2026
Same journal

UPF3A and UPF3B shape the transcriptome cooperatively yet oppose cell function.

Journal of molecular biology·2026
Same journal

Antibody-secreting cells integrate efficient NMD with non‑canonical UPR signaling to maintain proteostasis and support massive immunoglobulin synthesis.

Journal of molecular biology·2026
Same journal

Small molecule stabilization of diverse amyloidogenic immunoglobulin light chains revealed by hydrogen-deuterium exchange mass spectrometry.

Journal of molecular biology·2026
Same journal

UPF1 at Work: Structural and Mechanistic Insights Into a Master Regulator of Nonsense-Mediated mRNA Decay.

Journal of molecular biology·2026
Same journal

Structural basis for the pro-amyloidogenic action and ligand binding of a novel W72R variant of human apolipoprotein A-I.

Journal of molecular biology·2026
Same journal

Cryo-EM Structure of the C. Elegans Septin Tetramer Reveals a Revised Architecture and Conserved Positional Orthology.

Journal of molecular biology·2026
See all related articles

Determining enzyme function conservation requires careful analysis beyond simple sequence identity. While 40% identity may suffice for broad enzyme commission (EC) number transfer, 60% is needed for precise four-digit EC number accuracy.

Area of Science:

  • Biochemistry
  • Bioinformatics
  • Computational Biology

Background:

  • Enzyme function conservation is crucial for inferring protein function.
  • Previous studies proposed varying sequence identity thresholds (e.g., 40%) for function transfer, but these may be influenced by database bias.
  • Rost's work highlighted the need for family-based comparisons, suggesting divergence below 70% sequence identity.

Purpose of the Study:

  • To refine the sequence identity thresholds for reliable enzyme function transfer.
  • To investigate the impact of functional similarity alongside sequence similarity in enzyme classification.
  • To evaluate the correlation between E-values from PSI-BLAST and enzyme function conservation.

Main Methods:

  • Classified enzyme families based on both sequence and functional similarity (EC number).

Related Experiment Videos

  • Calculated and averaged function conservation across all enzyme families.
  • Analyzed the relationship between sequence identity thresholds and accuracy of EC number transfer.
  • Assessed the correlation between PSI-BLAST E-values and function conservation.

    • Main Results:

    • 40% sequence identity is a confident threshold for transferring the first three digits of an EC number.
    • Above 60% sequence identity is required for at least 90% accuracy in transferring all four digits of an EC number.
    • E-values from PSI-BLAST show a weak correlation with enzyme function conservation, suggesting caution in functional annotation.
    • Enzyme family-specific thresholds enable accurate functional inference but may miss some true positives below the threshold.

    Conclusions:

    • Enzyme function transfer requires nuanced sequence identity thresholds dependent on the desired level of functional specificity (EC number digits).
    • PSI-BLAST E-values should be interpreted cautiously for functional annotation due to weak correlation with conservation.
    • While family-specific thresholds enhance accuracy, they pose challenges in identifying all true positive sequences.