KpKP13 Protein target profile

Histidine ammonia-lyase

Accession: KP13_03022

Gene: AHE45594.1 hutH 3D evidence: AlphaFold DB model + ColabFold model UniProt A0A0H3GQG3
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Length 508
Pocket druggability (P2Rank · AlphaFold DB model) 0.637
Direct ligand evidence 0 59 total records
Functional annotation 1 EC 7 GO
Target summary

Promising target candidate with multiple supporting evidence streams.

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

Main supporting evidence

Core gene across strains Marked as conserved by both pan-genome tools: Roary and CoreCruncher. Moderate predicted binding pocket FPocket selected-pocket score 0.44. This supports review but is not experimental validation. Second pocket predictor agrees P2Rank predicted binding-site probability 0.64. Structure available AlphaFold DB model + ColabFold model Review the complete evidence below

Risks to review

Human similarity Top human hit identity: 50.34%. This target also has a predicted binding pocket (P2Rank 0.64) — check the ligand evidence before deprioritizing on off-target risk alone. Microbiome similarity 122 of 4744 screened genomes (2.6%) have a significant similarity hit. This target also has a predicted binding pocket (P2Rank 0.64) — check the ligand evidence before deprioritizing on off-target risk alone.

Evidence gaps

No metabolic context No SBML/network-derived reaction evidence is loaded for this protein.
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 (%)
50.34 Lower values reduce human off-target concern.
Human E-value
2.87e-36
Gut microbiome similarity
2.6% of screened genomes Lower prevalence suggests narrower overlap with the screened gut microbiome.

Essentiality

Essential (DEG)
Y
DEG identity (%)
82.143 Higher values support similarity to known essential genes.
DEG E-value
0.0 Smaller values mean stronger essential-gene similarity.

Structure confidence

ColabFold pLDDT
96.43 0-100 confidence; >70 supports local structural interpretation.

Binding-site evidence

AlphaFold DB / UniProt model

P2Rank's binding-site probability is the primary druggability signal shown across the app; FPocket's druggability score is shown alongside it for comparison. Both estimate small-molecule pocket quality after applying the curated structure priority — neither is experimental binding evidence. The 3D viewer may show a different loaded structure, so visible pockets can differ.

Druggability (P2Rank) 0.637
Structure A0A0H3GQG3
Pocket Pocket 1
Druggability (FPocket) 0.438
Structure A0A0H3GQG3
Pocket Pocket 18
ColabFold model
P2Rank 0.635 · Pocket 1
FPocket 0.521 · Pocket 3
Core conservation Conserved core gene
Roary core
CoreCruncher core
Gut microbiome 122 / 4744 genomes with a hit
Prevalence 2.6%

Sequence

Primary amino-acid sequence viewer.

MKSLTLIPGQLSLSQLRDVYSHPVNITLDSGAFAAIDESVACVNAILAEGRTAYGINTGFGLLAQTRISTEDLENLQRSLVLSHAAGVGEPLDDDLTRLIMVLKINSLSRGFSGIRLSVIQALIGLVNAGVTPWIPAKGSVGASGDLAPLAHMSLTLLGEGKARVRGGEWLPATEALRQVGLEPITLAAKEGLALLNGTQASTAFALRGLFEAEDLFASAVVCGALTTEAALGSRRPFDARIHEVRGQRGQIDAAALYRHLLTDDSAISQSHHNCSKVQDPYSLRCQPQVMGACLTQIRQAAEVLLAEANAVSDNPLVFAAENDVISGGNFHAEPVAMAADNIALAIAEIGSLSERRIALMMDSHMSQLPPFLVKNGGVNSGFMIAQVTAAALASENKALSHPHSVDSLPTSANQEDHVSMAPAAGRRLWAMAENTRGVLAVEWLAAAQGLDMREGLTTSPLLEEARHLLRERVPHYTQDRYFAPDIDNAIALLAARHLTRLLPAVLH

Functional annotations

Enzyme classification and Gene Ontology terms linked to this protein.

1 EC 7 GO

Subcellular localization

Localization
Cytoplasmic

Enzyme Commission (EC)

1

Gene Ontology (GO)

7
  • GO:0016841 Catalysis of the release of ammonia by the cleavage of a carbon-nitrogen bond or the reverse reaction with ammonia as a substrate.
  • GO:0005737 The contents of a cell excluding the plasma membrane and nucleus, but including other subcellular structures.
  • GO:0004397 Catalysis of the reaction: L-histidine = trans-urocanate + NH4+.
  • 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:0006548 The chemical reactions and pathways resulting in the breakdown of L-histidine.
  • GO:0019556 OBSOLETE. The chemical reactions and pathways resulting in the breakdown of L-histidine into other compounds, including glutamate and formamide.
  • GO:0019557 OBSOLETE. The chemical reactions and pathways resulting in the breakdown of L-histidine into other compounds, including glutamate and formate.

Sequence domains and features

Domain and signature matches imported from InterPro and related databases.

19 records
Show feature table
Start End DB Term Name
199 507 FunFam G3DSA:1.20.200.10:FF:000003 Histidine ammonia-lyase
9 454 CDD cd00332 PAL-HAL
9 454 InterPro IPR001106 Aromatic amino acid lyase
139 155 ProSitePatterns PS00488 Phenylalanine and histidine ammonia-lyases signature.
139 155 InterPro IPR022313 Phenylalanine/histidine ammonia-lyases, active site
11 472 Pfam PF00221 Aromatic amino acid lyase
11 472 InterPro IPR001106 Aromatic amino acid lyase
5 504 SUPERFAMILY SSF48557 L-aspartase-like
5 504 InterPro IPR008948 L-Aspartase-like
3 505 Hamap MF_00229 Histidine ammonia-lyase [hutH].
3 505 InterPro IPR005921 Histidine ammonia-lyase
6 504 NCBIfam TIGR01225 histidine ammonia-lyase
6 504 InterPro IPR005921 Histidine ammonia-lyase
199 507 Gene3D G3DSA:1.20.200.10 Fumarase/aspartase (Central domain)
9 455 PANTHER PTHR10362 HISTIDINE AMMONIA-LYASE
9 455 InterPro IPR001106 Aromatic amino acid lyase
2 198 Gene3D G3DSA:1.10.275.10 -
2 198 InterPro IPR024083 Fumarase/histidase, N-terminal
1 198 FunFam G3DSA:1.10.275.10:FF:000005 Histidine ammonia-lyase

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 · P2Rank

Druggability (P2Rank): high ≥ 0.5 · medium 0.2–0.49 · low < 0.2

Pocket 1 P2Rank #1
0.637
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Surrounding area
Pocket 2 P2Rank #2
0.057
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Surrounding area
Pocket 3 P2Rank #3
0.045
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Surrounding area
Pocket 4 P2Rank #4
0.027
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Surrounding area
Pocket 5 P2Rank #5
0.018
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Surrounding area

Binding pockets · FPocket

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

Pocket 1 FPocket #18
0.438
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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_A0A0H3GQG3
AlphaFold DB — — full sequence — Viewing
ColabFold KP13_03022
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.

59 records
Chemistry signal

Structural ligand evidence is available for this target.

Direct evidence 0 same-protein records
Transferred evidence 9 records from similar proteins
Structural ligands 9 0 loaded crystals
Measured bioactivity 0 direct and transferred ChEMBL records
Proposed compounds 50 similarity-based ZINC candidates
Best available ligand signal
247 PDB via homolog 217.2 Da · LogP 1.11 · TPSA 83.5 Open detail RCSB PDB
295 PDB via homolog Detail RCSB PDB
296 PDB via homolog Detail RCSB PDB
DHC PDB via homolog Detail RCSB PDB
HC4 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
247 RCSB PDB
2QVE
Q8GMG0 217.2 Da LogP 1.11 TPSA 83.5 ✓ Ro5 ✓ Clean c1cc(ccc1[C@H](C(C(=O)O)(F)F)N)O
295 RCSB PDB
2RJR
Q8GMG0 200.2 Da LogP 0.30 TPSA 77.8 ✓ Ro5 ✓ Clean c1cc(ccc1[C@@H]([C@@H](C(=O)O)O)O)F
296 RCSB PDB
2RJS
Q8GMG0 231.2 Da LogP 1.41 TPSA 72.5 ✓ Ro5 ✓ Clean COc1ccc(cc1)[C@H](C(C(=O)O)(F)F)N
DHC RCSB PDB
2O7D
Q3IWB0 180.2 Da LogP 1.20 TPSA 77.8 ✓ Ro5 Alert c1cc(c(cc1\C=C\C(=O)O)O)O
HC4 RCSB PDB
2O7B
Q3IWB0 164.2 Da LogP 1.49 TPSA 57.5 ✓ Ro5 ✓ Clean c1cc(ccc1/C=C/C(=O)O)O
KZ5 RCSB PDB
6S7Q
M2BPW8 263.3 Da LogP -0.79 TPSA 123.6 ✓ Ro5 ✓ Clean CN(C)[C@@H](Cc1c[nH]c(n1)S(=O)(=O)O)C(=O)O
PMI RCSB PDB
2O7E
Q3IWB0 213.2 Da LogP 0.62 TPSA 83.6 ✓ Ro5 ✓ Clean c1ccc2c(c1)CC(C2)(N)P(=O)(O)O
SFE RCSB PDB
3UNV
Q84FL5 165.2 Da LogP 1.16 TPSA 63.3 ✓ Ro5 ✓ Clean c1ccc(cc1)C(CC(=O)O)N
TCA RCSB PDB
2O78
Q3IWB0 148.2 Da LogP 1.78 TPSA 37.3 ✓ Ro5 ✓ Clean c1ccc(cc1)\C=C\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.

Cross-references

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

Sequence

UniProt A0A0H3GQG3