// Enzyme — ensemble-vs-static demonstration · Protein pipeline, Phase 6 evidence layer

TEM-1 β-lactamase

286 aa (P62593) · predicted structure regenerated live for this page (AlphaFold DB + ANM ensemble + fpocket + cross-frame ranker, same pipeline as every worked example on this site).

// Independently verified against a real PDB structure — not pipeline output

A different kind of finding: the rank-1 pocket only appears in later ANM ensemble frames (member frames 2-3 of 5), absent from the static AlphaFold structure. Cross-walked to the deposited PDB 1M40’s Ambler numbering, it lands on residues 99, 102-107, 110 — squarely inside the independently-published H3-loop-H4 allosteric region (Ambler 99-114), not the specific Bowman-lab cryptic pocket this target was originally chosen to test against. Structural check: whole-chain CA RMSD vs. 1M40 is 0.37 Å, crosswalk-matched over 262 of 286 residues — near-experimental accuracy.

Rank 1 Rank 2 Rank 3

// Sequence

MSIQHFRVALIPFFAAFCLPVFAHPETLVKVKDAEDQLGARVGYIELDLNSGKILESFRPEERFPMMSTFKVLLCGAVLSRVDAGQEQLGRRIHYSQNDLVEYSPVTEKHLTDGMTVRELCSAAITMSDNTAANLLLTTIGGPKELTAFLHNMGDHVTRLDRWEPELNEAIPNDERDTTMPAAMATTLRKLLTGELLTLASRQQLIDWMEADKVAGPLLRSALPAGWFIADKSGAGERGSRGIIAALGPDGKPSRIVVIYTTGSQATMDERNRQIAEIGASLIKHW
Length286 aa
UniProtP62593
Mean structure confidence0.9485
Pocket clusters3
Numbering cross-walk262/286 vs. 1M40

// Findings

Family, precedent, and provenance

Family classification

returned data

Beta-lactamase2 (PF13354) — Beta-lactamase enzyme family

E=1.20e-43 · bit score 149.9 · passes GA threshold: yes

Known ligand precedent

returned data

153 total structures in family · 9 distinct ligand scaffolds curated

  • 8RMAA1H1U
  • 6WJMALA
  • 8R2Y6M9
  • 8R2ZXR9
  • 7Q116V8

Conservation

returned data

56 seed sequences · mean pairwise identity 21.8%

Similar known proteins

returned data
  • 6NIQ43.2% identity · (none)
  • 6WJM36.4% identity · ALA
  • 5NE336.2% identity · NXL
  • 7D5J36.1% identity · (none)
  • 3W4P35.5% identity · (none)

Structure-based (Foldseek)

  • 7QOR — TM 1.000 · 100% id (new vs. sequence list)
  • 1JWV — TM 1.000 · 100% id (new vs. sequence list)
  • 1XXM — TM 1.000 · 99% id (new vs. sequence list)
  • 1FQG — TM 1.000 · 100% id (new vs. sequence list)
  • 6AYK — TM 1.000 · 99% id (new vs. sequence list)

Interaction fingerprints (Evidence Integration Layer)

no_ligand_bound_structure

8 ligand-bound structure(s) exist for this target's Pfam family (PF13354), but none checked aligned to the query at >=50% sequence coverage — likely other members of the same broad family, not this specific protein. Interaction fingerprints require a structure of the query protein itself.

Structural analysis — ranked pocket clusters

returned data

Residue numbers below are pipeline-sequential, with the literature (author-deposited PDB 1M40) number shown in parentheses — 262/286 residues cross-walked.

RankPersistenceResidues
#1139(41), 40(42), 41(43), 61(63), 62(64), 63(65), 65(67), 170(172), 171(173), 172(174), 173(175), 174(176), 175(177), 178(180), 180(?), 238(241), 262(266), 263(267), 264(268), 265(269)
#2120(?), 21(?), 22(?), 23(?), 24(26), 27(29), 46(48), 53(55), 54(56), 55(57), 56(58), 255(259), 282(286), 284(288), 285(289), 286(290)
#3161(63), 154(156), 155(157), 156(158), 157(159), 180(?), 182(184), 183(185), 186(188), 187(189), 190(192)

Pocket functional context (UniProt + ClinVar)

Pocket 1

no UniProt functional features or ClinVar variants overlap with pocket residues

Pocket 2

no UniProt functional features or ClinVar variants overlap with pocket residues

Pocket 3

no UniProt functional features or ClinVar variants overlap with pocket residues

// Limitations & data provenance

Auto-populated from each section’s own status — not hand-maintained.

Family classificationreturned data
Known ligand precedentreturned data
Interaction fingerprintsno_ligand_bound_structure
Functional contextreturned data
Conservationreturned data
Structural analysisreturned data
Similar known proteinsreturned data