// NMR / fragment screening · Protein pipeline, Phase 6 evidence layer
Carbonic anhydrase 2
260 aa (P00918) · 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
Independently checked against PDB 2CBA (catalytic zinc site). The rank-1 cluster (persistence 1.0) exactly matches the zinc-coordinating His94/His96/His119 triad plus four more real pocket-wall residues — a clean, correct hit on the second easy-case sanity anchor. Structural check: CA RMSD vs. 2CBA is 0.53 Å whole-chain, 0.29 Å within the pocket — the most accurate structural match in the batch.
// Sequence
// Findings
Family, precedent, and provenance
Family classification
returned dataCarb_anhydrase (PF00194) — Eukaryotic-type carbonic anhydrase
E=1.40e-94 · bit score 317.2 · passes GA threshold: yes
Known ligand precedent
returned data1429 total structures in family · 13 distinct ligand scaffolds curated
- 3K34 — HGB, SUA
- 5Y2S — CO2
- 6KLZ — BCT
- 6ROB — HG, BE7, KBZ, GLC, BGC
- 6SBL — HG, L4Q, BE7
Conservation
returned data250 seed sequences · mean pairwise identity 31.3%
Similar known proteins
returned data- 3K34 — 100.0% identity · HGB, SUA
- 3KS3 — 100.0% identity · (none)
- 5Y2S — 100.0% identity · CO2
- 4YXI — 100.0% identity · 4J8, MBO
- 4FPT — 100.0% identity · 0VZ, MBO
Structure-based (Foldseek)
- 1ZSC — TM 1.000 · 100% id (new vs. sequence list)
- 5JE7 — TM 1.000 · 100% id (new vs. sequence list)
- 3RYY — TM 1.000 · 100% id (new vs. sequence list)
- 2H4N — TM 1.000 · 100% id (new vs. sequence list)
- 6QL3 — TM 1.000 · 98% id (new vs. sequence list)
Interaction fingerprints (Evidence Integration Layer)
returned dataRepresentative complex: 3K34 (HGB, 0.90 Å)
| Residue (PDB) | Residue (pipeline) | Interaction | Partner |
|---|---|---|---|
| 138 | 137 | hydrophobic | PRO138 (hydrophobic) with ligand HGB |
Representative complex: 5Y2S (CO2, 0.90 Å)
| Residue (PDB) | Residue (pipeline) | Interaction | Partner |
|---|---|---|---|
| 199 | 198 | hydrogen bond | THR199 (hydrogen bond) with ligand CO2 |
| 200 | 199 | water bridge | THR200 (water bridge) with ligand CO2 |
| 200 | 199 | water bridge | THR200 (water bridge) with ligand CO2 |
| 92 | 92 | water bridge | GLN92 (water bridge) with ligand CO2 |
Representative complex: 6KLZ (BCT, 0.90 Å)
| Residue (PDB) | Residue (pipeline) | Interaction | Partner |
|---|---|---|---|
| 199 | 198 | hydrogen bond | THR199 (hydrogen bond) with ligand BCT |
| 119 | 119 | hydrogen bond | HIS119 (hydrogen bond) with ligand BCT |
| 199 | 198 | hydrogen bond | THR199 (hydrogen bond) with ligand BCT |
| 94 | 94 | water bridge | HIS94 (water bridge) with ligand BCT |
| 200 | 199 | water bridge | THR200 (water bridge) with ligand BCT |
| 92 | 92 | water bridge | GLN92 (water bridge) with ligand BCT |
| 92 | 92 | water bridge | GLN92 (water bridge) with ligand BCT |
| 92 | 92 | water bridge | GLN92 (water bridge) with ligand BCT |
| 92 | 92 | water bridge | GLN92 (water bridge) with ligand BCT |
Structural analysis — ranked pocket clusters
returned dataResidue numbers below are pipeline-sequential, with the literature (author-deposited PDB 3K34) number shown in parentheses — 258/260 residues cross-walked.
| Rank | Persistence | Residues |
|---|---|---|
| #1 | 1 | 5(5), 7(7), 62(62), 64(64), 65(65), 67(67), 91(91), 92(92), 94(94), 96(96), 119(119), 121(121), 130(131), 134(135), 140(141), 142(143), 196(197), 197(198), 198(199), 199(200) … |
| #2 | 1 | 3(3), 4(4), 5(5), 6(6), 7(7), 8(8), 11(11), 63(63), 64(64), 169(170), 230(231), 231(232), 232(233), 235(236), 236(237), 238(239), 239(240), 241(242) |
| #3 | 1 | 3(3), 4(4), 5(5), 9(9), 10(10), 11(11), 15(15), 16(16), 18(18), 19(19), 20(20) |
Pocket residues overlapping known interaction sites
- Pocket 1: residues 92, 94, 119, 198, 199 (5 of 24 pocket residues match a known interaction site)
- Pocket 2: no overlap with known interaction sites (18 checked)
- Pocket 3: no overlap with known interaction sites (11 checked)
Pocket functional context (UniProt + ClinVar)
Pocket 1
- Residue 7: Site — Fine-tunes the proton-transfer properties of H-64
- Residue 7: ClinVar variant [Pathogenic] — Y7* (NM_000067.3(CA2):c.21C>A (p.Tyr7Ter))
- Residue 62: Site — Fine-tunes the proton-transfer properties of H-64; involved in the binding of some activators, including histamine and L-histidine
- Residue 64: Active site — Proton donor/acceptor
- Residue 67: Site — Fine-tunes the proton-transfer properties of H-64; involved in the binding of some activators, including histamine and L-histidine
- Residue 92: Site — Involved in the binding of some activators, including histamine and L-histidine
- Residue 92: ClinVar variant [Likely pathogenic] — Q92P (NM_000067.3(CA2):c.275A>C (p.Gln92Pro))
- Residue 92: ClinVar variant [Likely pathogenic] — Y92* (NM_000067.3(CA2):c.579C>G (p.Tyr193Ter))
- Residue 94: Binding site — Binding site
- Residue 96: Binding site — Binding site
- Residue 119: Binding site — Binding site
- Residue 198: Binding site — Binding site
- Residue 199: Binding site — Binding site
- Residue 208: ClinVar variant [Pathogenic] — W208fs (NM_000067.3(CA2):c.621del (p.Trp208fs))
Pocket 2
- Residue 7: Site — Fine-tunes the proton-transfer properties of H-64
- Residue 7: ClinVar variant [Pathogenic] — Y7* (NM_000067.3(CA2):c.21C>A (p.Tyr7Ter))
- Residue 64: Active site — Proton donor/acceptor
- Residue 236: ClinVar variant [Pathogenic] — P236H (NM_000067.3(CA2):c.707C>A (p.Pro236His))
Pocket 3
- Residue 18: ClinVar variant [Pathogenic] — K18E (NM_000067.3(CA2):c.52A>G (p.Lys18Glu))
// Limitations & data provenance
Auto-populated from each section’s own status — not hand-maintained.