Enzymes: evolution of function from a structural perspective
Bibliographic record
Abstract
HIV-1 integrase catalyzes the insertion of viral DNA into the human chromosome, and as such, it is a target for the development of new anti-HIV drugs. Structural studies of HIV-1 integrase have been limited due to its insolubility. We have engineered a soluble, functional integrase by introducing five point mutations, and have solved the structure of the viral DNA binding core and C-terminal domains to 2.8 resolution. The Y-shaped, dimeric molecule reveals a putative DNA binding region consisting of residues contributed by both monomers of the dimer. This implies that a dimer is the minimal DNA binding unit. A kink at T210 occurs at a proteolytic cleavage site, suggesting a functional flexibility in the molecule that may be crucial for integration. The C-terminal domain is an SH3-like fold, and provides the majority of the crystal contacts, consistent with the role of the domain in oligomerization of integrase. Based on this structure, we are outlining new strategies to discover novel drug leads targeting integrase.
Fetched live from OpenAlex and de-inverted. Abstracts are not stored in this database: the inverted indexes are 8.6 GB of the frame’s 9.3 GB of text, and the host has 13 GB free.
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 | 0.001 |
| Bibliometrics | 0.001 | 0.002 |
| 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".