Amino acids
523
Annotations
9
Features
30
PDB binders
7
Druggability
0.206
Overview
Basic information about this protein and its source genome.
- Accession
- VK055_2493
- Gene
- AIK81090.1 leuA
- Status
- annotated
- Amino acids
- 523
- Structure source
- AlphaFold + ColabFold
EC
GO
GO:0003824 Catalysis of a biochemical reaction at physiological temperatures. In biologically catalyzed reactions, the reactants are known as substrates, and the catalysts are naturally occurring macromolecular substances known as enzymes. Enzymes possess specific binding sites for substrates, and are usually composed wholly or largely of protein, but RNA that has catalytic activity (ribozyme) is often also regarded as enzymatic.
GO:0003852 Catalysis of the reaction: 3-methyl-2-oxobutanoate + acetyl-CoA + H2O = (2S)-2-isopropylmalate + CoA + H+.
GO:0009098 The chemical reactions and pathways resulting in the formation of L-leucine, 2-amino-4-methylpentanoic acid.
GO:0019752 The chemical reactions and pathways involving carboxylic acids, any organic acid containing one or more carboxyl (COOH) groups or anions (COO-).
GO:0046912 Catalysis of the transfer of an acyl group from one compound (donor) to another (acceptor), with the acyl group being converted into alkyl on transfer.
GO:0005829 The part of the cytoplasm that does not contain organelles but which does contain other particulate matter, such as protein complexes.
Target profile
Computed evidence for target prioritization.
- Human off-target
- hit
- Human identity (%)
- 25.0
- Human E-value
- 5.45e-07
- Gut microbiome off-target
- hit
- Essential (DEG)
- Y
- DEG identity (%)
- 66.996
- DEG E-value
- 0.0
- Localization
- Cytoplasmic
- ColabFold pLDDT
- 88.55
Selected Druggability evidence
AlphaFold / UniProt modelSelected Druggability is the FPocket score chosen for ranking using the curated structure priority. The 3D viewer may show a different loaded structure, so its visible pockets can differ.
FPocket
0.206
P2Rank
0.777
ColabFold model
Core conservation
Conserved core gene
Gut microbiome
344 / 4744
genomes with a hit
Sequence
Primary amino-acid sequence viewer.
Functional Annotations
Enzyme classification and Gene Ontology terms linked to this protein.
1 EC
8 GO
Enzyme Commission (EC)
1Gene Ontology (GO)
8- GO:0003824 Catalysis of a biochemical reaction at physiological temperatures. In biologically catalyzed reactions, the reactants are known as substrates, and the catalysts are naturally occurring macromolecular substances known as enzymes. Enzymes possess specific binding sites for substrates, and are usually composed wholly or largely of protein, but RNA that has catalytic activity (ribozyme) is often also regarded as enzymatic.
- GO:0003852 Catalysis of the reaction: 3-methyl-2-oxobutanoate + acetyl-CoA + H2O = (2S)-2-isopropylmalate + CoA + H+.
- GO:0009098 The chemical reactions and pathways resulting in the formation of L-leucine, 2-amino-4-methylpentanoic acid.
- GO:0019752 The chemical reactions and pathways involving carboxylic acids, any organic acid containing one or more carboxyl (COOH) groups or anions (COO-).
- GO:0046912 Catalysis of the transfer of an acyl group from one compound (donor) to another (acceptor), with the acyl group being converted into alkyl on transfer.
- GO:0005829 The part of the cytoplasm that does not contain organelles but which does contain other particulate matter, such as protein complexes.
- GO:0003985 Catalysis of the reaction: 2 acetyl-CoA = CoA + acetoacetyl-CoA.
- GO:0030145 Binding to a manganese ion (Mn).
Sequence Features
Domain/signature hits from InterPro and related databases.
30 records
Show feature table
| Start | End | DB | Term | Name |
|---|---|---|---|---|
| 502 | 523 | Coils | Coil | Coil |
| 280 | 392 | Gene3D | G3DSA:1.10.238.260 | - |
| 4 | 273 | Pfam | PF00682 | HMGL-like |
| 4 | 273 | InterPro | IPR000891 | Pyruvate carboxyltransferase |
| 1 | 279 | Gene3D | G3DSA:3.20.20.70 | Aldolase class I |
| 1 | 279 | InterPro | IPR013785 | Aldolase-type TIM barrel |
| 394 | 500 | FunFam | G3DSA:3.30.160.270:FF:000001 | 2-isopropylmalate synthase |
| 1 | 290 | SUPERFAMILY | SSF51569 | Aldolase |
| 2 | 509 | Hamap | MF_01025 | 2-isopropylmalate synthase [leuA]. |
| 2 | 509 | InterPro | IPR005671 | 2-isopropylmalate synthase, bacterial-type |
| 1 | 279 | FunFam | G3DSA:3.20.20.70:FF:000010 | 2-isopropylmalate synthase |
| 12 | 28 | ProSitePatterns | PS00815 | Alpha-isopropylmalate and homocitrate synthases signature 1. |
| 12 | 28 | InterPro | IPR002034 | Alpha-isopropylmalate/homocitrate synthase, conserved site |
| 7 | 275 | CDD | cd07940 | DRE_TIM_IPMS |
| 393 | 501 | Gene3D | G3DSA:3.30.160.270 | - |
| 393 | 501 | InterPro | IPR036230 | 2-isopropylmalate synthase LeuA, allosteric (dimerisation) domain superfamily |
| 3 | 501 | PANTHER | PTHR10277 | HOMOCITRATE SYNTHASE-RELATED |
| 199 | 212 | ProSitePatterns | PS00816 | Alpha-isopropylmalate and homocitrate synthases signature 2. |
| 199 | 212 | InterPro | IPR002034 | Alpha-isopropylmalate/homocitrate synthase, conserved site |
| 280 | 393 | FunFam | G3DSA:1.10.238.260:FF:000001 | 2-isopropylmalate synthase |
| 391 | 499 | SUPERFAMILY | SSF110921 | 2-isopropylmalate synthase LeuA, allosteric (dimerisation) domain |
| 391 | 499 | InterPro | IPR036230 | 2-isopropylmalate synthase LeuA, allosteric (dimerisation) domain superfamily |
| 5 | 267 | ProSiteProfiles | PS50991 | Pyruvate carboxyltransferase domain. |
| 5 | 267 | InterPro | IPR000891 | Pyruvate carboxyltransferase |
| 369 | 499 | Pfam | PF08502 | LeuA allosteric (dimerisation) domain |
| 369 | 499 | InterPro | IPR013709 | 2-isopropylmalate synthase LeuA, allosteric (dimerisation) domain |
| 369 | 500 | SMART | SM00917 | LeuA_dimer_2 |
| 369 | 500 | InterPro | IPR013709 | 2-isopropylmalate synthase LeuA, allosteric (dimerisation) domain |
| 4 | 497 | NCBIfam | TIGR00973 | 2-isopropylmalate synthase |
| 4 | 497 | InterPro | IPR005671 | 2-isopropylmalate synthase, bacterial-type |
3D Structure
Selected loaded structure. Experimental PDB entries may cover only a portion of the sequence; predicted models typically cover the full protein.
Loading 3D structure...
Legend
High
Medium
Low
Structural evidence
0 + 2Experimental PDB entries and predicted models. Click Switch to display a different structure in the viewer.
| Entry | Method | Resolution | Chain | Coverage | Links | Status |
|---|---|---|---|---|---|---|
|
AlphaFold
AF_A0A0H3GJ80
|
AlphaFold | — | — | full sequence | — | Viewing |
|
ColabFold
VK055_2493
|
ColabFold | — | — | full sequence | — | Loaded |
Pocket details FPocket · P2Rank — toggle visibility and zoom from here, or open full viewer
Pockets (FPOCKET)
Showing top-ranked FPocket candidates by druggability. Druggability is color-coded: high (0.7 or higher), medium (0.4 to 0.69), low (below 0.4).
| FPOCKET | Sticks | Spheres | Surfaces | Druggability | Labels | Zoom | Positions |
|---|---|---|---|---|---|---|---|
| 38 | 0.206 |
Pockets (P2RANK)
Showing top-ranked P2Rank candidates by probability. Probability is color-coded per P2Rank calibration: high (≥ 0.5), medium (0.2 – 0.49), low (< 0.2).
| P2RANK | Sticks | Spheres | Surfaces | Score | Probability | Labels | Zoom | Positions |
|---|---|---|---|---|---|---|---|---|
| 1 | 15.19 | 0.748 | ||||||
| 2 | 4.15 | 0.168 | ||||||
| 3 | 1.81 | 0.034 | ||||||
| 4 | 1.66 | 0.028 |
Pockets (FPOCKET)
Showing top-ranked FPocket candidates by druggability. Druggability is color-coded: high (0.7 or higher), medium (0.4 to 0.69), low (below 0.4).
| FPOCKET | Sticks | Spheres | Surfaces | Druggability | Labels | Zoom | Positions |
|---|---|---|---|---|---|---|---|
| 3 | 0.285 |
Pockets (P2RANK)
Showing top-ranked P2Rank candidates by probability. Probability is color-coded per P2Rank calibration: high (≥ 0.5), medium (0.2 – 0.49), low (< 0.2).
| P2RANK | Sticks | Spheres | Surfaces | Score | Probability | Labels | Zoom | Positions |
|---|---|---|---|---|---|---|---|---|
| 1 | 12.3 | 0.646 | ||||||
| 2 | 2.24 | 0.055 | ||||||
| 3 | 2.0 | 0.043 | ||||||
| 4 | 1.52 | 0.022 | ||||||
| 5 | 1.08 | 0.007 |
Ligand evidence
Ligands grouped by evidence source. PDB ligands keep the source crystal visible, and loaded crystals can be opened directly in the structure viewer.
57 records
Highest-confidence structural evidence: ligands co-crystallized with this exact protein. If the source PDB is loaded in TPW, use Open crystal to inspect it in the structure viewer.
No PDB structure with a co-crystallized ligand found for this exact protein.
Structural evidence inferred from similar proteins. The source crystal indicates where the ligand was observed; the UniProt column identifies the homologous protein carrying that ligand.
| Ligand | Source crystal | UniProt (homolog) | MW · LogP · TPSA | Lipinski | PAINS | SMILES |
|---|---|---|---|---|---|---|
| AKG | O87198 | 146.1 Da LogP -0.50 TPSA 91.7 | ✓ Ro5 | ✓ Clean |
C(CC(=O)O)C(=O)C(=O)O
|
|
| HCA | O87198 | 206.1 Da LogP -0.86 TPSA 132.1 | ✓ Ro5 | ✓ Clean |
C(C[C@@](CC(=O)O)(C(=O)O)O)C(=O)O
|
|
| KIV | B0SN40 | 116.1 Da LogP 0.30 TPSA 54.4 | ✓ Ro5 | ✓ Clean |
CC(C)C(=O)C(=O)O
|
|
| KMT | C5J4P1 | 148.2 Da LogP 0.39 TPSA 54.4 | ✓ Ro5 | ✓ Clean |
CSCCC(=O)C(=O)O
|
|
| MLI | Q8F3Q1 | 102.0 Da LogP -3.12 TPSA 80.3 | ✓ Ro5 | ✓ Clean |
C(C(=O)[O-])C(=O)[O-]
|
|
| PYR | Q8F3Q1 | 88.1 Da LogP -0.34 TPSA 54.4 | ✓ Ro5 | ✓ Clean |
CC(=O)C(=O)O
|
|
| VPM | B0SN40 | 176.2 Da LogP -0.07 TPSA 94.8 | ✓ Ro5 | ✓ Clean |
CC(C)[C@@](CC(=O)O)(C(=O)O)O
|
Experimental bioactivity from ChEMBL measured directly on this protein. Score = pchembl (−log Ki/IC₅₀; higher = more potent).
No ChEMBL bioactivity data found for this exact protein.
Bioactivity inferred from similar proteins in ChEMBL. Score = pchembl (−log Ki/IC₅₀; higher = more potent).
No ChEMBL hits found through similar proteins.
Proposed virtual-screening candidates from ZINC. Score = Tanimoto similarity to a known binder (0–1; higher = more similar).
| Ligand | Tanimoto | MW · LogP · TPSA | Lipinski | PAINS | SMILES |
|---|---|---|---|---|---|
| ZINC2572371 | 0.680 | 206.1 Da LogP -1.00 TPSA 132.1 | ✓ Ro5 | ✓ Clean |
C[C@@H](C(=O)O)[C@@](O)(CC(=O)O)C(=O)O
|
| ZINC2572383 | 0.680 | 206.1 Da LogP -1.00 TPSA 132.1 | ✓ Ro5 | ✓ Clean |
C[C@H](C(=O)O)[C@@](O)(CC(=O)O)C(=O)O
|
| ZINC3869734 | 0.680 | 206.1 Da LogP -1.00 TPSA 132.1 | ✓ Ro5 | ✓ Clean |
C[C@H](C(=O)O)[C@](O)(CC(=O)O)C(=O)O
|
| ZINC901307 | 0.680 | 206.1 Da LogP -1.00 TPSA 132.1 | ✓ Ro5 | ✓ Clean |
C[C@@H](C(=O)O)[C@](O)(CC(=O)O)C(=O)O
|
| ZINC2384798 | 0.607 | 202.3 Da LogP -0.05 TPSA 92.4 | ✓ Ro5 | ✓ Clean |
CC[C@H](C)[C@H](N)C(=O)N[C@@H](C)C(=O)O
|
| ZINC146315135 | 0.593 | 204.2 Da LogP 0.86 TPSA 94.8 | ✓ Ro5 | ✓ Clean |
CCCCC[C@@](O)(CC(=O)O)C(=O)O
|
| ZINC146315336 | 0.593 | 204.2 Da LogP 0.86 TPSA 94.8 | ✓ Ro5 | ✓ Clean |
CCCCC[C@](O)(CC(=O)O)C(=O)O
|
| ZINC2391059 | 0.586 | 244.3 Da LogP 0.98 TPSA 92.4 | ✓ Ro5 | ✓ Clean |
CC[C@H](C)[C@H](N)C(=O)N[C@H](C(=O)O)[C@@H](C)CC
|
| ZINC40472549 | 0.586 | 244.3 Da LogP 0.98 TPSA 92.4 | ✓ Ro5 | ✓ Clean |
CC[C@H](C)[C@H](N)C(=O)N[C@@H](C(=O)O)[C@@H](C)…
|
| ZINC40490721 | 0.586 | 244.3 Da LogP 0.98 TPSA 92.4 | ✓ Ro5 | ✓ Clean |
CC[C@H](C)[C@@H](NC(=O)[C@@H](N)[C@H](C)CC)C(=O…
|
| ZINC5909388 | 0.586 | 244.3 Da LogP 0.98 TPSA 92.4 | ✓ Ro5 | ✓ Clean |
CC[C@H](C)[C@H](NC(=O)[C@@H](N)[C@H](C)CC)C(=O)O
|
| ZINC1726452 | 0.571 | 220.2 Da LogP -0.61 TPSA 132.1 | ✓ Ro5 | ✓ Clean |
CC[C@@H](C(=O)O)[C@@](O)(CC(=O)O)C(=O)O
|
| ZINC1726453 | 0.571 | 220.2 Da LogP -0.61 TPSA 132.1 | ✓ Ro5 | ✓ Clean |
CC[C@H](C(=O)O)[C@@](O)(CC(=O)O)C(=O)O
|
| ZINC1726454 | 0.571 | 220.2 Da LogP -0.61 TPSA 132.1 | ✓ Ro5 | ✓ Clean |
CC[C@@H](C(=O)O)[C@](O)(CC(=O)O)C(=O)O
|
| ZINC1726455 | 0.571 | 220.2 Da LogP -0.61 TPSA 132.1 | ✓ Ro5 | ✓ Clean |
CC[C@H](C(=O)O)[C@](O)(CC(=O)O)C(=O)O
|
| ZINC4899467 | 0.567 | 230.3 Da LogP 0.59 TPSA 92.4 | ✓ Ro5 | ✓ Clean |
CC[C@H](C)[C@H](N)C(=O)N[C@H](C(=O)O)C(C)C
|
| ZINC5662848 | 0.567 | 230.3 Da LogP 0.59 TPSA 92.4 | ✓ Ro5 | ✓ Clean |
CC[C@@H](C)[C@H](N)C(=O)N[C@H](C(=O)O)C(C)C
|
| ZINC5662849 | 0.567 | 230.3 Da LogP 0.59 TPSA 92.4 | ✓ Ro5 | ✓ Clean |
CC[C@@H](C)[C@@H](N)C(=O)N[C@H](C(=O)O)C(C)C
|
| ZINC5662850 | 0.567 | 230.3 Da LogP 0.59 TPSA 92.4 | ✓ Ro5 | ✓ Clean |
CC[C@H](C)[C@@H](N)C(=O)N[C@H](C(=O)O)C(C)C
|
| ZINC3634656 | 0.556 | 210.1 Da LogP -1.30 TPSA 132.1 | ✓ Ro5 | ✓ Clean |
O=C(O)C[C@](O)(C(=O)O)[C@H](F)C(=O)O
|
| ZINC3634658 | 0.556 | 210.1 Da LogP -1.30 TPSA 132.1 | ✓ Ro5 | ✓ Clean |
O=C(O)C[C@@](O)(C(=O)O)[C@H](F)C(=O)O
|
| ZINC3634659 | 0.556 | 210.1 Da LogP -1.30 TPSA 132.1 | ✓ Ro5 | ✓ Clean |
O=C(O)C[C@](O)(C(=O)O)[C@@H](F)C(=O)O
|
| ZINC3634661 | 0.556 | 210.1 Da LogP -1.30 TPSA 132.1 | ✓ Ro5 | ✓ Clean |
O=C(O)C[C@@](O)(C(=O)O)[C@@H](F)C(=O)O
|
| ZINC255963942 | 0.548 | 357.5 Da LogP 1.51 TPSA 121.5 | ✓ Ro5 | ✓ Clean |
CC[C@H](C)[C@H](N)C(=O)N[C@H](C(=O)N[C@H](C(=O)…
|
| ZINC255963943 | 0.548 | 357.5 Da LogP 1.51 TPSA 121.5 | ✓ Ro5 | ✓ Clean |
CC[C@H](C)[C@H](N)C(=O)N[C@H](C(=O)N[C@H](C(=O)…
|
| ZINC2560984 | 0.548 | 246.3 Da LogP -0.60 TPSA 129.7 | ✓ Ro5 | ✓ Clean |
CC[C@@H](C)[C@@H](N)C(=O)N[C@@H](CC(=O)O)C(=O)O
|
| ZINC2575119 | 0.548 | 218.3 Da LogP -1.08 TPSA 112.7 | ✓ Ro5 | ✓ Clean |
CC[C@H](C)[C@H](N)C(=O)N[C@@H](CO)C(=O)O
|
| ZINC39831468 | 0.548 | 357.5 Da LogP 1.51 TPSA 121.5 | ✓ Ro5 | ✓ Clean |
CC[C@H](C)[C@H](N)C(=O)N[C@H](C(=O)N[C@H](C(=O)…
|
| ZINC4762961 | 0.548 | 357.5 Da LogP 1.51 TPSA 121.5 | ✓ Ro5 | ✓ Clean |
CC[C@H](C)[C@H](N)C(=O)N[C@H](C(=O)N[C@H](C(=O)…
|
| ZINC13529436 | 0.533 | 212.3 Da LogP 1.76 TPSA 46.3 | ✓ Ro5 | ✓ Clean |
CC[C@H](C)[C@H](N)C(=O)N1CCCCCC1
|
| ZINC1726446 | 0.533 | 234.2 Da LogP -0.22 TPSA 132.1 | ✓ Ro5 | ✓ Clean |
CCC[C@@H](C(=O)O)[C@@](O)(CC(=O)O)C(=O)O
|
| ZINC1726447 | 0.533 | 234.2 Da LogP -0.22 TPSA 132.1 | ✓ Ro5 | ✓ Clean |
CCC[C@H](C(=O)O)[C@@](O)(CC(=O)O)C(=O)O
|
| ZINC1726448 | 0.533 | 234.2 Da LogP -0.22 TPSA 132.1 | ✓ Ro5 | ✓ Clean |
CCC[C@@H](C(=O)O)[C@](O)(CC(=O)O)C(=O)O
|
| ZINC1726449 | 0.533 | 234.2 Da LogP -0.22 TPSA 132.1 | ✓ Ro5 | ✓ Clean |
CCC[C@H](C(=O)O)[C@](O)(CC(=O)O)C(=O)O
|
| ZINC19502834 | 0.533 | 212.3 Da LogP 1.76 TPSA 46.3 | ✓ Ro5 | ✓ Clean |
CC[C@@H](C)[C@@H](N)C(=O)N1CCCCCC1
|
| ZINC19502836 | 0.533 | 212.3 Da LogP 1.76 TPSA 46.3 | ✓ Ro5 | ✓ Clean |
CC[C@H](C)[C@@H](N)C(=O)N1CCCCCC1
|
| ZINC19502838 | 0.533 | 212.3 Da LogP 1.76 TPSA 46.3 | ✓ Ro5 | ✓ Clean |
CC[C@@H](C)[C@H](N)C(=O)N1CCCCCC1
|
| ZINC13508097 | 0.531 | 234.3 Da LogP -0.14 TPSA 92.4 | ✓ Ro5 | ✓ Clean |
CC[C@H](C)[C@H](N)C(=O)N[C@@H](CS)C(=O)O
|
| ZINC2556613 | 0.531 | 244.3 Da LogP 0.98 TPSA 92.4 | ✓ Ro5 | ✓ Clean |
CC[C@H](C)[C@H](N)C(=O)N[C@@H](CC(C)C)C(=O)O
|
| ZINC11959312 | 0.516 | 213.3 Da LogP 0.13 TPSA 49.6 | ✓ Ro5 | ✓ Clean |
CC[C@@H](C)[C@H](N)C(=O)N1CCN(C)CC1
|
| ZINC11959315 | 0.516 | 213.3 Da LogP 0.13 TPSA 49.6 | ✓ Ro5 | ✓ Clean |
CC[C@H](C)[C@H](N)C(=O)N1CCN(C)CC1
|
| ZINC19504598 | 0.516 | 213.3 Da LogP 0.13 TPSA 49.6 | ✓ Ro5 | ✓ Clean |
CC[C@@H](C)[C@@H](N)C(=O)N1CCN(C)CC1
|
| ZINC19504599 | 0.516 | 213.3 Da LogP 0.13 TPSA 49.6 | ✓ Ro5 | ✓ Clean |
CC[C@H](C)[C@@H](N)C(=O)N1CCN(C)CC1
|
| ZINC2390958 | 0.516 | 230.3 Da LogP 0.59 TPSA 92.4 | ✓ Ro5 | ✓ Clean |
CC[C@H](C)[C@H](NC(=O)[C@@H](N)C(C)C)C(=O)O
|
| ZINC40472548 | 0.516 | 230.3 Da LogP 0.59 TPSA 92.4 | ✓ Ro5 | ✓ Clean |
CC[C@@H](C)[C@@H](NC(=O)[C@@H](N)C(C)C)C(=O)O
|
| ZINC8577168 | 0.516 | 230.3 Da LogP 0.59 TPSA 92.4 | ✓ Ro5 | ✓ Clean |
CC[C@H](C)[C@@H](NC(=O)[C@@H](N)C(C)C)C(=O)O
|
| ZINC2522618 | 0.515 | 245.3 Da LogP -1.20 TPSA 135.5 | ✓ Ro5 | ✓ Clean |
CC[C@H](C)[C@H](N)C(=O)N[C@@H](CC(N)=O)C(=O)O
|
| ZINC3593496 | 0.500 | 206.2 Da LogP -1.16 TPSA 121.1 | ✓ Ro5 | ✓ Clean |
COC(=O)C[C@@](O)(CC(=O)O)C(=O)O
|
| ZINC3593497 | 0.500 | 206.2 Da LogP -1.16 TPSA 121.1 | ✓ Ro5 | ✓ Clean |
COC(=O)C[C@](O)(CC(=O)O)C(=O)O
|
| ZINC8577157 | 0.500 | 202.3 Da LogP -0.05 TPSA 92.4 | ✓ Ro5 | ✓ Clean |
CC[C@H](C)[C@@H](NC(=O)[C@H](C)N)C(=O)O
|
PDB and ChEMBL records on this protein are shown in full. ChEMBL records from similar proteins are capped at the top 100 per protein (by pchembl) and ZINC at the top 50 (Tanimoto ≥ 0.5). ADME columns are descriptor-based screening flags, not experimental toxicity results.