Protein target profile

VK055_0134

fumarylacetoacetate hydrolase domain-containing protein 1

Genome: KpATCC43816 Gene: fahHD1 AIK78762.1 3D evidence: AlphaFold DB model + ColabFold model Metabolism 1 reaction UniProt A0A0H3GVA6
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Length 219
Pocket druggability 0.456
Metabolic reactions 1
Chokepoint Yes
Direct ligand evidence 0 18 total records
Functional annotation 0 EC 3 GO
Target summary

Strong target candidate with converging metabolic, structural and chemical evidence.

Automated synthesis of the evidence currently loaded. Review the underlying records before prioritizing this protein.

Main supporting evidence

Metabolic bottleneck Catalyzes a reaction that is the only producer or consumer of a metabolite in the imported metabolic model. Central metabolic position More central than 92.2% of genes in this genome. No isoenzyme backup detected Imported GPR rules do not show an alternative enzyme for the catalyzed reaction set. Moderate predicted binding pocket FPocket selected-pocket score 0.46. This supports review but is not experimental validation. Review the complete evidence below

Risks to review

Human similarity Top human hit identity: 46.465%. This target also has a predicted binding pocket (FPocket 0.46) — check the ligand evidence before deprioritizing on off-target risk alone. Microbiome similarity 115 of 4744 screened genomes (2.4%) have a significant similarity hit. This target also has a predicted binding pocket (FPocket 0.46) — check the ligand evidence before deprioritizing on off-target risk alone. Mixed conservation Core/accessory calls are not fully concordant.

Evidence coverage

Core evidence streams are available for this target.
Terms and data sources used on this page

PDB: experimentally determined structures from the Protein Data Bank. These are the strongest structural evidence, but may cover only part of the protein.

AlphaFold DB model: a precomputed predicted structure downloaded from AlphaFold Database/UniProt, not an experiment performed here.

ColabFold model: a predicted structure generated for this workspace; interpret it with coverage and confidence.

pLDDT: confidence score for predicted structures. High values support local geometry; low values mean the region should not drive pocket interpretation.

FPocket / P2Rank: software tools that predict possible ligand-binding pockets on a 3D structure. They are useful screening signals, not experimental validation.

Druggability: a pocket-based estimate of whether a small molecule could bind productively. It does not mean a drug already exists.

PDB ligand: a compound observed in an experimental structure. Direct same-protein records are stronger than homolog-transferred records.

ChEMBL: a public database of measured compound bioactivity. Direct entries are stronger than entries transferred from similar proteins.

ZINC: a purchasable-compound database. Here it marks proposed candidates from chemical similarity, not measured binders.

LigQ / LigQ_2: an internal Target pipeline step that gathers PDB, ChEMBL, and ZINC ligand evidence for each protein.

Off-target: sequence similarity to proteins we prefer not to hit, such as human proteins or beneficial gut microbiome proteins.

DEG: Database of Essential Genes. A match suggests the protein resembles genes known to be essential in other organisms.

Roary / CoreCruncher: pan-genome tools used to decide whether a gene is core across analyzed strains or accessory/strain-specific.

EC / GO: functional annotations: EC describes enzyme reactions; GO describes biological process, molecular function, or cellular component.

KEGG pathway: a curated metabolic route label used here to group reactions imported from the metabolic model.

Chokepoint: a metabolic reaction that is the only producer or consumer of a metabolite in the imported model.

Prioritization evidence

Selectivity, essentiality, structural confidence, conservation, and predicted binding-site evidence.

Off-target risk

Human off-target
Hit
Human identity (%)
46.465 Lower values reduce human off-target concern.
Human E-value
1.95e-62
Gut microbiome similarity
2.4% of screened genomes Lower prevalence suggests narrower overlap with the screened gut microbiome.

Essentiality

Essential (DEG)
Y
DEG identity (%)
86.758 Higher values support similarity to known essential genes.
DEG E-value
1.53e-145 Smaller values mean stronger essential-gene similarity.

Localization

Localization
Cytoplasmic

Structure confidence

ColabFold pLDDT
97.07 0-100 confidence; >70 supports local structural interpretation.

Binding-site evidence

AlphaFold DB / UniProt model

The selected pocket score is the FPocket value used for ranking after applying the curated structure priority. It estimates small-molecule pocket quality; it is not experimental binding evidence. The 3D viewer may show a different loaded structure, so visible pockets can differ.

FPocket 0.456
Structure A0A0H3GVA6
Pocket Pocket 2
P2Rank 0.8
Structure A0A0H3GVA6
Pocket Pocket 1
ColabFold model
FPocket 0.285 · Pocket 4
P2Rank 0.786 · Pocket 1
Core conservation Accessory gene
Roary core
CoreCruncher accessory
Gut microbiome 115 / 4744 genomes with a hit
Prevalence 2.4%

Cross-references

External database identifiers for this protein, its structures, ligands, and metabolic reactions.

Sequence

UniProt A0A0H3GVA6

Pathways

KEGG R01364 BioCyc FUMARYLACETOACETASE-RXN

Metabolic context

Reactions catalyzed, pathway membership, and centrality in the genome-scale metabolic network.

Explore metabolic network

Attractive metabolic target: catalyzes a consuming chokepoint reaction in Styrene degradation, no isoenzyme backup detected, more central than 92.2% of genes in this genome.

Relative network centrality 92.2% more central than 92.2% of genes in this genome
Chokepoint Chokepoint gene
Pathways
Styrene degradation Tyrosine metabolism
Catalyzed reaction

1 reaction mapped to this gene in the metabolic model. Open the full network to see each one, with substrates/products and the reaction-reaction map.

Imported from KpATCC43816.sbml · 2026-07-09

Sequence

Primary amino-acid sequence viewer.

MYQHHNWQGALLDYPVSKVVCVGSNYAKHIKEMGSATPEEPVLFIKPETALCDLRQPLVLPEGLGSVHHEVELAVLIGSTLRQATEEHVLKGIAGYGVALDLTLRDLQAKMKKAGQPWEKAKGFDNACPISGFIPAAEFHGDPQNTSLSLKINGEVRQQGTTADMIHRIVPLIAYMSRFFTLKAGDVILTGTPEGVGPLHSGDELEVGFNGLALTTRVL

Functional annotations

Enzyme classification and Gene Ontology terms linked to this protein.

3 GO

Gene Ontology (GO)

3
  • 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:0018773 Catalysis of the reaction: acetylpyruvate + H2O = acetate + H+ + pyruvate.
  • GO:0046872 Binding to a metal ion.

Sequence domains and features

Domain and signature matches imported from InterPro and related databases.

8 records
Show feature table
Start End DB Term Name
11 212 PANTHER PTHR11820 ACYLPYRUVASE
11 213 SUPERFAMILY SSF56529 FAH
11 213 InterPro IPR036663 Fumarylacetoacetase-like, C-terminal domain superfamily
1 219 Gene3D G3DSA:3.90.850.10 -
1 219 InterPro IPR036663 Fumarylacetoacetase-like, C-terminal domain superfamily
1 219 FunFam G3DSA:3.90.850.10:FF:000007 Fumarylacetoacetate hydrolase family protein
18 213 Pfam PF01557 Fumarylacetoacetate (FAA) hydrolase family
18 213 InterPro IPR011234 Fumarylacetoacetase-like, C-terminal

3D structure

Selected loaded structure. Experimental PDB entries may cover only a portion of the sequence; AlphaFold DB and ColabFold models typically cover the full protein but remain computational predictions.

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Pocket score High Medium Low
How colors and pocket overlays are used
Uniform protein color marks the displayed model as a single molecular object.
Experimental PDB structures may be colored by chain to distinguish subunits or copies present in the file.
Pocket colors and alpha spheres are evidence overlays for predicted binding cavities; they are not alternative protein chains.
'Alpha spheres' is FPocket's own cavity-shape geometry, imported when available and aligned with the loaded structure.
'Pocket atoms'/'Predicted site atoms' show the pocket's residue atoms instead: P2Rank reports residues rather than alpha spheres, and FPocket falls back to this when alpha-sphere geometry is unavailable or doesn't align.
'No pocket geometry' means neither alpha spheres nor residue-position data could be found for that pocket; the layer just highlights the same residues as 'Nearby residues'.
Pocket details Inspect a specific pocket, or open the full viewer

Binding pockets · FPocket

Druggability: high ≥ 0.7 · medium 0.4–0.69 · low < 0.4

Site 1 FPocket #2
0.456
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Surrounding area

Binding pockets · P2Rank

Probability: high ≥ 0.5 · medium 0.2–0.49 · low < 0.2

Site 1 P2Rank #1
0.8
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Surrounding area
Site 2 P2Rank #2
0.016
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Surrounding area
Site 3 P2Rank #3
0.005
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Surrounding area
All structural evidence 0 experimental · 2 predicted

Structural evidence

0 + 2

Experimental PDB entries plus predicted AlphaFold DB or ColabFold models. Click Switch to display a different loaded structure in the viewer.

Entry Method Resolution Chain Coverage Links Status
AlphaFold DB AF_A0A0H3GVA6
AlphaFold DB — — full sequence — Viewing
ColabFold VK055_0134
ColabFold — — full sequence — Loaded

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.

18 records
Chemistry signal

Structural ligand evidence is available for this target.

Direct evidence 0 same-protein records
Transferred evidence 3 records from similar proteins
Structural ligands 3 0 loaded crystals
Measured bioactivity 0 direct and transferred ChEMBL records
Proposed compounds 15 similarity-based ZINC candidates
Best available ligand signal
OXL PDB via homolog 88.0 Da · LogP -3.51 · TPSA 80.3 Open detail RCSB PDB
PYR PDB via homolog Detail RCSB PDB
TAR PDB via homolog Detail RCSB PDB
ZINC12359024 ZINC proposed compound · Tanimoto 0.692 Detail ZINC
ZINC13533920 ZINC proposed compound · Tanimoto 0.692 Detail ZINC

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.

Show only:
Ligand Source crystal UniProt (homolog) MW · LogP · TPSA Lipinski PAINS SMILES
OXL RCSB PDB
6FOG
Q6P587-1 88.0 Da LogP -3.51 TPSA 80.3 ✓ Ro5 ✓ Clean C(=O)(C(=O)[O-])[O-]
PYR RCSB PDB
6J5X
Q8NLC0 88.1 Da LogP -0.34 TPSA 54.4 ✓ Ro5 ✓ Clean CC(=O)C(=O)O
TAR RCSB PDB
3V77
D2YW46 150.1 Da LogP -2.12 TPSA 115.1 ✓ Ro5 ✓ Clean [C@H]([C@@H](C(=O)O)O)(C(=O)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.