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Atlas — TEM-1 β-lactamase

UniProt: P62593 Gene symbol: bla (TEM) Protein: β-lactamase TEM Organism: Escherichia coli (taxonomy ID 562) Disease (MONDO): not applicable — this is a pathogen drug-resistance enzyme, not a host disease gene. Adjacent ontology: NCBIT taxon 562; DOID:0050486 (drug-resistant infection). Disease class: infectious-disease drug-resistance target (not a Mendelian disease); class A serine β-lactamase.

Question this atlas entry answers

A medicinal-chemistry team scopes a β-lactamase inhibitor program. They need: the catalytic machinery (Ser-70 nucleophile + the oxyanion hole + the general base), the Sec-system signal peptide and mature-chain boundaries, and the structural evidence (many-PDB-structures-of-the-canonical-enzyme story).

Tool sequence

# Tool Question
1 uniprot_search("protein_name:\"Beta-lactamase TEM\" AND organism_id:562 AND reviewed:true", size=1) Confirm canonical accession (P62593).
2 uniprot_get_entry("P62593") Function (β-lactam hydrolysis), 286 aa, periplasmic localisation.
3 uniprot_get_active_sites("P62593") The headline tool: Ser-70 (nucleophile), Glu-166 (general base), Lys-234 (oxyanion stabilisation), Ser-130 (substrate binding).
4 uniprot_get_processing_features("P62593") 23-aa Sec signal peptide; mature chain residues 24–286.
5 uniprot_get_ptms("P62593") Empty advisory — bacterial Sec-secreted enzymes typically have no curated PTMs (the empty advisory points at PhosphoSitePlus / GlyConnect for completeness).
6 uniprot_resolve_pdb("P62593") Many high-resolution structures; canonical 1BTL at 1.80 Å, 1JTG at 1.73 Å, etc.
7 uniprot_resolve_chembl("P62593") β-lactamase inhibitors (clavulanate, sulbactam, tazobactam) and avibactam-class diazabicyclooctanes.

Expected response shape

  • Step 3: at least four Active site / Binding site annotations clustered in the active-site cleft (Ser-70, Glu-166, Lys-234, Ser-130).
  • Step 4: Signal peptide 1–23 + Chain 24–286.
  • Step 5: 0 feature(s) with the honest empty advisory pointing at PhosphoSitePlus / GlyConnect — bacterial periplasmic enzymes are typically PTM-free.
  • Step 6: 30+ PDB structures; the best at 1.73 Å (1JTG).

Therapeutic axis (interpretation)

  • β-lactamase inhibitors — small molecules that occupy the active site and prevent β-lactam hydrolysis. Three "classical" inhibitors (clavulanate, sulbactam, tazobactam) form a covalent acyl-enzyme intermediate at Ser-70 that is more stable than the productive hydrolytic intermediate.
  • Newer-generation inhibitors: diazabicyclooctanes (avibactam, relebactam, durlobactam) — reversible covalent binders; boronate-based (vaborbactam, taniborbactam) — transition-state mimics.
  • Class shift: TEM-1 is a class A serine β-lactamase. Carbapenemases (KPC, NDM, OXA, IMP) and metallo-β-lactamases (NDM-1) require different inhibitor chemistries — but the active-site geometry tool surfaces those mechanism differences.
  • ChEMBL bridge: β-lactamase is a richly-populated target with small-molecule, peptide, and natural-product inhibitors.

Provenance fields

Standard envelope on every response.

Cross-references in scope

Resource Returned via
PDB Many high-resolution apo and inhibitor-bound structures.
AlphaFold DB AF-P62593-F1 (very high confidence over the entire fold).
ChEMBL Rich; clavulanate, sulbactam, tazobactam, avibactam, vaborbactam, relebactam, more.
InterPro Class A β-lactamase signature (PF00144 etc.).

Adjacent ontologies

Ontology Identifier
NCBI taxonomy 562 (E. coli)
ARO (CARD) ARO:3000014 (TEM-1) — the Antibiotic Resistance Ontology canonical entry
DOID DOID:0050486 (drug-resistant infection)

Why TEM-1

TEM-1 is the canonical infectious-disease drug-target case. It demonstrates that the same uniprot_get_active_sites / uniprot_get_processing_features / uniprot_get_ptms workflow that handles human enzymes (PAH) also handles pathogen enzymes — the tool surface is organism-agnostic. The empty PTM advisory is honest and informative for a bacterial periplasmic enzyme.