Structural basis for substrate specificity and catalysis of human histone acetyltransferase 1
Bibliographic record
Abstract
Histone acetyltransferase 1 is the founding member of the histone acetyltransferase superfamily and catalyzes lysine acetylation of newly synthesized histone H4. Here we report a 1.9-Å resolution crystal structure of human histone acetyltransferase 1 in complex with acetyl coenzyme A and histone H4 peptide. The crystal structure reveals that the cofactor and the side chain of lysine 12 of histone H4 peptide are placed in the canyon between the central and C-terminal domains. Histone H4 peptide adopts a well-defined conformation and establishes an extensive set of interactions with the enzyme including invariant residues Glu64 and Trp199, which together govern substrate-binding specificity of histone acetyltransferase 1. Our structure-guided enzyme kinetic study further demonstrates a cumulative effect of the active-site residues Glu187, Glu276, and Asp277 on deprotonation of the ε-amino group of reactive Lys12 for direct attack of the acetyl group of the cofactor.
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How this classification was reachedexpand
Full frame distilled prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. Learned from the 10,348 direct Codex labels and 10,348 direct Gemma labels. Candidate is the union of thresholded teacher heads; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels or direct frontier model labels.
Codex and Gemma teacher scores by category
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.000 | 0.000 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.000 | 0.000 |
| Bibliometrics | 0.000 | 0.000 |
| Science and technology studies | 0.000 | 0.000 |
| Scholarly communication | 0.000 | 0.000 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.000 | 0.000 |
| Insufficient payload (model declined to judge) | 0.000 | 0.000 |
Machine scores (provisional)
The two teacher heads of the student model, read on this work. A score orders the frame for review; it never asserts a category, and the validation status ships verbatim with every row.
Baseline scores from an immature model (maturity gate not passed, 7 training rounds). Scores rank; they never assert a category.
score_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from itClassification
machine, unvalidatedMachine predicted; a candidate call from one teacher head, not a consensus.
How this classification was reached, model by model and score by score, is at the end of the page under "How this classification was reached".