Protein target profile

VK055_5040

1-(5-phosphoribosyl)-5-[(5- phosphoribosylamino)methylideneamino]imidazole-4- carboxamide isomerase

Genome: KpATCC43816 Gene: hisA AIK83566.1 3D evidence: AlphaFold DB model + ColabFold model Metabolism 1 reaction UniProt A0A0H3H0J1
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Length 245
Pocket druggability 0.968
Metabolic reactions 1
Chokepoint Yes
Direct ligand evidence 0 56 total records
Functional annotation 1 EC 4 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 96.2% 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

Microbiome similarity 173 of 4744 screened genomes (3.6%) have a significant similarity hit. This target also has a predicted binding pocket (FPocket 0.97) — check the ligand evidence before deprioritizing on off-target risk alone. Best pocket may be a modeling artifact FPocket selected-pocket score 0.97, but this pocket's geometry is unusually large/diffuse compared to this protein's other predicted pockets — may reflect a low-confidence or disordered model region rather than a real cavity.

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
3.6% of screened genomes Lower prevalence suggests narrower overlap with the screened gut microbiome.

Essentiality

Essential (DEG)
Y
DEG identity (%)
63.673 Higher values support similarity to known essential genes.
DEG E-value
6.55e-114 Smaller values mean stronger essential-gene similarity.

Localization

Localization
Cytoplasmic

Structure confidence

ColabFold pLDDT
95.68 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 0.968
Structure A0A0H3H0J1
Pocket Pocket 1
P2Rank 0.991
Structure A0A0H3H0J1
Pocket Pocket 1
ColabFold model
FPocket 0.467 · Pocket 2
P2Rank 0.991 · Pocket 1
Core conservation Conserved core gene
Roary core
CoreCruncher core
Gut microbiome 173 / 4744 genomes with a hit
Prevalence 3.6%

Cross-references

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

Sequence

UniProt A0A0H3H0J1

Pathways

KEGG R04640 BioCyc PRIBFAICARPISOM-RXN

Metabolic context

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

Explore metabolic network

Attractive metabolic target: catalyzes a producing & consuming chokepoint reaction in Histidine metabolism, no isoenzyme backup detected, more central than 96.2% of genes in this genome, no human homolog detected.

Relative network centrality 96.2% more central than 96.2% of genes in this genome
Chokepoint Chokepoint gene
Pathways
Histidine 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.

MIIPALDLIDGTVVRLHQGDYGQQRDYGSDPLPRLQAYAAQGAEVLHLVDLTGAKDPAKRQIPLLKSLVAGVDVPVQVGGGVRTEADVAALLEAGVARVVVGSTAVKSPEEVKGWFKRFGPERLVLALDVRIDADGNKQVAVSGWQENSGVTLEELVESYLPVGLQHVLCTDISRDGTLAGSNVSLYEEVCARYPQVAFQSSGGIGDLKDIAALRGTGVRGVIVGRALLEGKFNVTEAIQCWQNG

Functional annotations

Enzyme classification and Gene Ontology terms linked to this protein.

1 EC 4 GO

Enzyme Commission (EC)

1

Gene Ontology (GO)

4
  • GO:0000105 The chemical reactions and pathways resulting in the formation of L-histidine, 2-amino-3-(1H-imidazol-4-yl)propanoic acid.
  • GO:0003949 Catalysis of the reaction: 1-(5-phosphoribosyl)-5-[(5-phosphoribosylamino)methylideneamino]imidazole-4-carboxamide = 5-[(5-phospho-1-deoxy-D-ribulos-1-ylimino)methylamino]-1-(5-phospho-D-ribosyl)imidazole-4-carboxamide.
  • GO:0005737 The contents of a cell excluding the plasma membrane and nucleus, but including other subcellular structures.
  • GO:0000162 The chemical reactions and pathways resulting in the formation of L-tryptophan, the chiral amino acid 2-amino-3-(1H-indol-3-yl)propanoic acid; L-tryptophan is synthesized from chorismate via anthranilate.

Sequence domains and features

Domain and signature matches imported from InterPro and related databases.

15 records
Show feature table
Start End DB Term Name
1 243 SUPERFAMILY SSF51366 Ribulose-phoshate binding barrel
1 243 InterPro IPR011060 Ribulose-phosphate binding barrel
1 241 Hamap MF_01014 1-(5-phosphoribosyl)-5-[(5-phosphoribosylamino)methylideneamino] imidazole-4-carboxamide isomerase [hisA].
1 241 InterPro IPR023016 HisA/PriA, bacterial-type
2 242 PANTHER PTHR43090 1-(5-PHOSPHORIBOSYL)-5-[(5-PHOSPHORIBOSYLAMINO)METHYLIDENEAMINO] IMIDAZOLE-4-CARBOXAMIDE ISOMERASE
2 242 InterPro IPR044524 Histidine biosynthesis, HisA-like
1 233 Pfam PF00977 Histidine biosynthesis protein
1 233 InterPro IPR006062 Histidine biosynthesis protein
2 238 NCBIfam TIGR00007 1-(5-phosphoribosyl)-5-[(5-phosphoribosylamino)methylideneamino]imidazole-4-carboxamide isomerase
2 238 InterPro IPR006063 HisA, bacterial-type
1 245 Gene3D G3DSA:3.20.20.70 Aldolase class I
1 245 InterPro IPR013785 Aldolase-type TIM barrel
1 240 CDD cd04732 HisA
1 240 InterPro IPR023016 HisA/PriA, bacterial-type
1 244 FunFam G3DSA:3.20.20.70:FF:000009 1-(5-phosphoribosyl)-5-[(5-phosphoribosylamino)methylideneamino] imidazole-4-carboxamide isomerase

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 #1
0.968
Likely same site as P2Rank 1 1.1 Å 33 shared residues 94% of smaller site
Unusual size
Show in viewer
Surrounding area

Binding pockets · P2Rank

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

Site 1 P2Rank #1
0.991
Likely same site as FPocket 1 1.1 Å 33 shared residues 94% of smaller site
Show in viewer
Surrounding area
Site 2 P2Rank #2
0.06
Show in viewer
Surrounding area
Residue sets
UniProt: Active site:129-129 Proton donor
UniProt: Active site:7-7 Proton acceptor
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_A0A0H3H0J1
AlphaFold DB — — full sequence — Viewing
ColabFold VK055_5040
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.

56 records
Chemistry signal

Structural ligand evidence is available for this target.

Direct evidence 0 same-protein records
Transferred evidence 6 records from similar proteins
Structural ligands 6 0 loaded crystals
Measured bioactivity 0 direct and transferred ChEMBL records
Proposed compounds 50 similarity-based ZINC candidates
Best available ligand signal
137 PDB via homolog 351.2 Da · LogP -1.01 · TPSA 176.8 Open detail RCSB PDB
1PR PDB via homolog Detail RCSB PDB
2ER PDB via homolog Detail RCSB PDB
AMZ PDB via homolog Detail RCSB PDB
CXS PDB via homolog Detail RCSB PDB

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
137 RCSB PDB
2Y85
P9WMM5 351.2 Da LogP -1.01 TPSA 176.8 1 viol. ✓ Clean c1ccc(c(c1)C(=O)O)NC[C@H]([C@@H]([C@@H](COP(=O)…
1PR RCSB PDB
3ZS4
P9WMM5 581.4 Da LogP -5.14 TPSA 328.9 3 viol. ✓ Clean c1nc(c(n1[C@H]2[C@@H]([C@@H]([C@H](O2)COP(=O)(O…
2ER RCSB PDB
5AB3
P10372 577.3 Da LogP -4.45 TPSA 326.0 3 viol. ✓ Clean c1nc(c(n1[C@H]2[C@@H]([C@@H]([C@H](O2)COP(=O)(O…
AMZ RCSB PDB
4TX9
B5I4P8 338.2 Da LogP -2.71 TPSA 203.4 1 viol. ✓ Clean c1nc(c(n1[C@H]2[C@@H]([C@@H]([C@H](O2)COP(=O)(O…
CXS RCSB PDB
4X2R
C0W7K4 221.3 Da LogP 1.19 TPSA 66.4 ✓ Ro5 ✓ Clean C1CCC(CC1)NCCCS(=O)(=O)O
GUO RCSB PDB
5A5W
P10372 577.3 Da LogP -4.48 TPSA 318.2 3 viol. ✓ Clean c1nc(c(n1[C@H]2[C@@H]([C@@H]([C@H](O2)COP(=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.