Protein target profile

VK055_0342

2-keto-4-pentenoate hydratase

Genome: KpATCC43816 Gene: AIK78968.1 mhpD 3D evidence: AlphaFold DB model + ColabFold model Metabolism 3 reactions UniProt A0A0H3GZB7

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Length 269

Pocket druggability 0.911

Metabolic reactions 3

Chokepoint Yes

Direct ligand evidence 0 53 total records

Functional annotation 1 EC 6 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 92.0% of genes in this genome. No isoenzyme backup detected Imported GPR rules do not show an alternative enzyme for the catalyzed reaction set. No similar human protein detected The current BLAST sequence screen did not find a significant human match, lowering apparent off-target risk. Review the complete evidence below

Risks to review

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: No hit
Gut microbiome similarity: 0.8% of screened genomes Lower prevalence suggests narrower overlap with the screened gut microbiome.

Essentiality

Essential (DEG): N
DEG identity (%): 0.0 Higher values support similarity to known essential genes.

Localization

Localization: Cytoplasmic

Structure confidence

ColabFold pLDDT: 95.47 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 0.911

Structure A0A0H3GZB7

Pocket Pocket 2

P2Rank 0.798

Structure A0A0H3GZB7

Pocket Pocket 1

ColabFold model

FPocket 0.803 · Pocket 4

P2Rank 0.868 · Pocket 1

Core conservation Conserved core gene

Roary core

CoreCruncher core

Gut microbiome 36 / 4744 genomes with a hit

Prevalence 0.8%

Cross-references

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

Sequence

UniProt A0A0H3GZB7

Pathways

BioCyc RXN-10381 BioCyc RXN-20764 KEGG R02601 BioCyc 2-OXOPENT-4-ENOATE-HYDRATASE-RXN

Metabolic context

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

Explore metabolic network

Attractive metabolic target: catalyzes a producing chokepoint reaction in Benzoate degradation, no isoenzyme backup detected, more central than 92.0% of genes in this genome, no human homolog detected.

Relative network centrality 92.0% more central than 92.0% of genes in this genome

Chokepoint Chokepoint gene

Imported from KpATCC43816.sbml · 2026-07-09

Sequence

Primary amino-acid sequence viewer.

MMTFSLDALARQLRDAEQSGQAIAPLRNILGVDNADAAYAIQRLNVQHHVAHGRRVVGRKVGLTHPKVQQQLGVNQPDFGTLFADMCYGDNAEVPFGRVLQPKVEAEIALVLKQDLPHADTTFDELYNAIEWVLPALEVVGSRIRDWSIGFVDTVADNASCGLYVIGGPAQRPAGLDLKQCAMHMTRNQELVSSGRGSECLGHPLNAAVWLARKLASLGEPLRAGDIVLTGALGPMVTINKGDSFVAHIEGIGSVAARFVAAGEGDRDA

Functional annotations

Enzyme classification and Gene Ontology terms linked to this protein.

1 EC 6 GO

Enzyme Commission (EC)

4.2.1.80

Gene Ontology (GO)

GO:0008684 Catalysis of the reaction: 4-hydroxy-2-oxopentanoate = 2-oxopent-4-enoate + H2O.
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:0030145 Binding to a manganese ion (Mn).
GO:0019439 OBSOLETE. The chemical reactions and pathways resulting in the breakdown of aromatic compounds, any substance containing an aromatic carbon ring.
GO:0005737 The contents of a cell excluding the plasma membrane and nucleus, but including other subcellular structures.
GO:0019380 The chemical reactions and pathways resulting in the breakdown of 3-phenylpropionate, the anion of phenylpropanoic acid.

Sequence domains and features

Domain and signature matches imported from InterPro and related databases.

9 records

Show feature table

Start	End	DB	Term	Name
1	260	Hamap	MF_01655	2-keto-4-pentenoate hydratase [mhpD].
1	260	InterPro	IPR023793	2-keto-4-pentenoate hydratase
1	260	PANTHER	PTHR30143	ACID HYDRATASE
73	259	Pfam	PF01557	Fumarylacetoacetate (FAA) hydrolase family
73	259	InterPro	IPR011234	Fumarylacetoacetase-like, C-terminal
3	260	SUPERFAMILY	SSF56529	FAH
3	260	InterPro	IPR036663	Fumarylacetoacetase-like, C-terminal domain superfamily
3	265	Gene3D	G3DSA:3.90.850.10	-
3	265	InterPro	IPR036663	Fumarylacetoacetase-like, C-terminal domain superfamily

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

0.911

Likely same site as P2Rank 1 2.2 Å 17 shared residues 77% of smaller site

Unusual size

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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

0.798

Likely same site as FPocket 2 2.2 Å 17 shared residues 77% of smaller site

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Surrounding area

Site 2 P2Rank #2

0.338

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Surrounding area

Site 3 P2Rank #3

0.027

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Surrounding area

Site 4 P2Rank #4

0.003

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Surrounding area

Site 5 P2Rank #5

0.002

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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

0.868

Likely same site as FPocket 4 4.1 Å 17 shared residues 89% of smaller site

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Surrounding area

Site 2 P2Rank #2

0.252

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Surrounding area

Site 3 P2Rank #3

0.035

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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_A0A0H3GZB7	AlphaFold DB	—	—	full sequence	—	Viewing
ColabFold VK055_0342	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.

53 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 50 similarity-based ZINC candidates

Best available ligand signal

0L1 PDB via homolog 146.1 Da · LogP 0.72 · TPSA 74.6 Open detail RCSB PDB

AKG PDB via homolog Detail RCSB PDB

OOG PDB via homolog Detail RCSB PDB

ZINC1529497 ZINC proposed compound · Tanimoto 0.917 Detail ZINC

ZINC1531045 ZINC proposed compound · Tanimoto 0.917 Detail ZINC

Highest-confidence structural evidence: ligands co-crystallized with this exact protein. If the source PDB is loaded in Target, 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
0L1 RCSB PDB	5D2J	Q1XGK3	146.1 Da LogP 0.72 TPSA 74.6	✓ Ro5	✓ Clean	`C(CCC(=O)O)CC(=O)O`
AKG RCSB PDB	5D2H	Q1XGK3	146.1 Da LogP -0.50 TPSA 91.7	✓ Ro5	✓ Clean	`C(CC(=O)O)C(=O)C(=O)O`
OOG RCSB PDB	5D2K	Q1XGK3	160.1 Da LogP -0.11 TPSA 91.7	✓ Ro5	✓ Clean	`C(CC(=O)C(=O)O)CC(=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
ZINC1529497 ZINC	0.917	230.3 Da LogP 3.06 TPSA 74.6	✓ Ro5	✓ Clean	`O=C(O)CCCCCCCCCCC(=O)O`
ZINC1531045 ZINC	0.917	202.2 Da LogP 2.28 TPSA 74.6	✓ Ro5	✓ Clean	`O=C(O)CCCCCCCCC(=O)O`
ZINC1593115 ZINC	0.917	216.3 Da LogP 2.67 TPSA 74.6	✓ Ro5	✓ Clean	`O=C(O)CCCCCCCCCC(=O)O`
ZINC1700020 ZINC	0.917	244.3 Da LogP 3.45 TPSA 74.6	✓ Ro5	✓ Clean	`O=C(O)CCCCCCCCCCCC(=O)O`
ZINC3860440 ZINC	0.917	258.4 Da LogP 3.84 TPSA 74.6	✓ Ro5	✓ Clean	`O=C(O)CCCCCCCCCCCCC(=O)O`
ZINC3861298 ZINC	0.917	286.4 Da LogP 4.62 TPSA 74.6	✓ Ro5	✓ Clean	`O=C(O)CCCCCCCCCCCCCCC(=O)O`
ZINC5113062 ZINC	0.917	272.4 Da LogP 4.23 TPSA 74.6	✓ Ro5	✓ Clean	`O=C(O)CCCCCCCCCCCCCC(=O)O`
ZINC2508031 ZINC	0.786	230.3 Da LogP 1.85 TPSA 91.7	✓ Ro5	✓ Clean	`O=C(O)CCCCC(=O)CCCCC(=O)O`
ZINC26897400 ZINC	0.733	286.4 Da LogP 3.41 TPSA 91.7	✓ Ro5	✓ Clean	`O=C(O)CCCCCCC(=O)CCCCCCC(=O)O`
ZINC3074813 ZINC	0.733	258.3 Da LogP 2.63 TPSA 91.7	✓ Ro5	✓ Clean	`O=C(O)CCCCCC(=O)CCCCCC(=O)O`
ZINC34423725 ZINC	0.733	342.5 Da LogP 4.97 TPSA 91.7	✓ Ro5	✓ Clean	`O=C(O)CCCCCCCCC(=O)CCCCCCCCC(=O)O`
ZINC4822898 ZINC	0.733	272.3 Da LogP 3.02 TPSA 91.7	✓ Ro5	✓ Clean	`O=C(O)CCCCCCC(=O)CCCCCC(=O)O`
ZINC4822900 ZINC	0.733	300.4 Da LogP 3.80 TPSA 91.7	✓ Ro5	✓ Clean	`O=C(O)CCCCCCCCC(=O)CCCCCC(=O)O`
ZINC13433578 ZINC	0.688	201.3 Da LogP 1.68 TPSA 80.4	✓ Ro5	✓ Clean	`NC(=O)CCCCCCCCC(=O)O`
ZINC14510370 ZINC	0.688	244.4 Da LogP 3.74 TPSA 57.5	✓ Ro5	✓ Clean	`O=C(O)CCCCCCCCCCCCCO`
ZINC1531061 ZINC	0.688	216.3 Da LogP 2.96 TPSA 57.5	✓ Ro5	✓ Clean	`O=C(O)CCCCCCCCCCCO`
ZINC1610426 ZINC	0.688	230.3 Da LogP 3.35 TPSA 57.5	✓ Ro5	✓ Clean	`O=C(O)CCCCCCCCCCCCO`
ZINC2168567 ZINC	0.688	202.3 Da LogP 2.57 TPSA 57.5	✓ Ro5	✓ Clean	`O=C(O)CCCCCCCCCCO`
ZINC3074815 ZINC	0.688	230.3 Da LogP 1.85 TPSA 91.7	✓ Ro5	✓ Clean	`O=C(O)CCCCCC(=O)CCCC(=O)O`
ZINC3861297 ZINC	0.688	272.4 Da LogP 4.52 TPSA 57.5	✓ Ro5	✓ Clean	`O=C(O)CCCCCCCCCCCCCCCO`
ZINC4284502 ZINC	0.688	258.4 Da LogP 4.13 TPSA 57.5	✓ Ro5	✓ Clean	`O=C(O)CCCCCCCCCCCCCCO`
ZINC5287109 ZINC	0.688	286.5 Da LogP 4.91 TPSA 57.5	✓ Ro5	✓ Clean	`O=C(O)CCCCCCCCCCCCCCCCO`
ZINC1703342 ZINC	0.667	202.2 Da LogP 1.07 TPSA 91.7	✓ Ro5	✓ Clean	`O=C(O)CCCC(=O)CCCC(=O)O`
ZINC115371230 ZINC	0.647	266.4 Da LogP 2.88 TPSA 74.6	✓ Ro5	✓ Clean	`O=C(O)CCCCSSCCCCC(=O)O`
ZINC12954423 ZINC	0.647	232.4 Da LogP 3.90 TPSA 37.3	✓ Ro5	✓ Clean	`O=C(O)CCCCCCCCCCCS`
ZINC13357569 ZINC	0.647	243.4 Da LogP 3.71 TPSA 63.3	✓ Ro5	✓ Clean	`NCCCCCCCCCCCCCC(=O)O`
ZINC138216182 ZINC	0.647	293.2 Da LogP 4.76 TPSA 37.3	✓ Ro5	✓ Clean	`O=C(O)CCCCCCCCCCCCBr`
ZINC14619253 ZINC	0.647	214.3 Da LogP 3.17 TPSA 54.4	✓ Ro5	✓ Clean	`CC(=O)CCCCCCCCCC(=O)O`
ZINC1529498 ZINC	0.647	200.3 Da LogP 3.99 TPSA 37.3	✓ Ro5	✓ Clean	`CCCCCCCCCCCC(=O)O`
ZINC1530417 ZINC	0.647	228.4 Da LogP 4.77 TPSA 37.3	✓ Ro5	✓ Clean	`CCCCCCCCCCCCCC(=O)O`
ZINC1628119 ZINC	0.647	214.3 Da LogP 4.38 TPSA 37.3	✓ Ro5	✓ Clean	`CCCCCCCCCCCCC(=O)O`
ZINC1661158 ZINC	0.647	234.3 Da LogP 2.23 TPSA 74.6	✓ Ro5	✓ Clean	`O=C(O)CCCCSCCCCC(=O)O`
ZINC1763117 ZINC	0.647	201.3 Da LogP 2.54 TPSA 63.3	✓ Ro5	✓ Clean	`NCCCCCCCCCCC(=O)O`
ZINC1841307 ZINC	0.647	228.3 Da LogP 3.56 TPSA 54.4	✓ Ro5	✓ Clean	`CC(=O)CCCCCCCCCCC(=O)O`
ZINC1845814 ZINC	0.647	215.3 Da LogP 2.93 TPSA 63.3	✓ Ro5	✓ Clean	`NCCCCCCCCCCCC(=O)O`
ZINC1845839 ZINC	0.647	200.3 Da LogP 2.78 TPSA 54.4	✓ Ro5	✓ Clean	`CC(=O)CCCCCCCCC(=O)O`
ZINC2164257 ZINC	0.647	218.4 Da LogP 3.51 TPSA 37.3	✓ Ro5	✓ Clean	`O=C(O)CCCCCCCCCCS`
ZINC22048354 ZINC	0.647	229.4 Da LogP 3.32 TPSA 63.3	✓ Ro5	✓ Clean	`NCCCCCCCCCCCCC(=O)O`
ZINC33822328 ZINC	0.647	270.4 Da LogP 4.73 TPSA 54.4	✓ Ro5	✓ Clean	`CC(=O)CCCCCCCCCCCCCC(=O)O`
ZINC34552398 ZINC	0.647	257.4 Da LogP 4.10 TPSA 63.3	✓ Ro5	✓ Clean	`NCCCCCCCCCCCCCCC(=O)O`
ZINC34628306 ZINC	0.647	271.4 Da LogP 4.49 TPSA 63.3	✓ Ro5	✓ Clean	`NCCCCCCCCCCCCCCCC(=O)O`
ZINC35465466 ZINC	0.647	244.3 Da LogP 2.24 TPSA 91.7	✓ Ro5	✓ Clean	`O=C(O)CCCCCCCC(=O)CCC(=O)O`
ZINC5855130 ZINC	0.647	242.4 Da LogP 3.95 TPSA 54.4	✓ Ro5	✓ Clean	`CC(=O)CCCCCCCCCCCC(=O)O`
ZINC90745150 ZINC	0.647	260.4 Da LogP 4.68 TPSA 37.3	✓ Ro5	✓ Clean	`O=C(O)CCCCCCCCCCCCCS`
ZINC2579544 ZINC	0.611	207.1 Da LogP 2.54 TPSA 37.3	✓ Ro5	✓ Clean	`C=C(Br)CCCCC(=O)O`
ZINC4789573 ZINC	0.611	310.4 Da LogP 4.62 TPSA 74.6	✓ Ro5	✓ Clean	`O=C(O)CCCCCCCC#CCCCCCCCC(=O)O`
ZINC5501162 ZINC	0.611	350.5 Da LogP 4.52 TPSA 74.6	✓ Ro5	✓ Clean	`O=C(O)CCCCSCCCCCCSCCCCC(=O)O`
ZINC139104910 ZINC	0.579	270.4 Da LogP 4.73 TPSA 54.4	✓ Ro5	✓ Clean	`CCC(=O)CCCCCCCCCCCCC(=O)O`
ZINC2151107 ZINC	0.579	231.3 Da LogP 1.60 TPSA 100.6	✓ Ro5	✓ Clean	`NC(CCCCC(=O)O)CCCCC(=O)O`
ZINC4823272 ZINC	0.579	256.4 Da LogP 4.34 TPSA 54.4	✓ Ro5	✓ Clean	`CCC(=O)CCCCCCCCCCCC(=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.