KpATCC43816 Protein target profile

aconitate hydratase 2

Accession: VK055_2445

Gene: AIK81042.1 acnB 3D evidence: AlphaFold DB model + ColabFold model Metabolism 4 reactions UniProt A0A0H3GJE4

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Length 839

Pocket druggability (P2Rank · AlphaFold DB model) 0.873

Metabolic reactions 4

Chokepoint No

Direct ligand evidence 0 25 total records

Functional annotation 2 EC 8 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

Central metabolic position More central than 95.9% of genes in this genome. No similar human protein detected The current BLAST sequence screen did not find a significant human match, lowering apparent off-target risk. Core gene across strains Marked as conserved by both pan-genome tools: Roary and CoreCruncher. Second pocket predictor agrees P2Rank predicted binding-site probability 0.87. 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: 4.8% of screened genomes Lower prevalence suggests narrower overlap with the screened gut microbiome.

Essentiality

Essential (DEG): Y
DEG identity (%): 96.782 Higher values support similarity to known essential genes.
DEG E-value: 0.0 Smaller values mean stronger essential-gene similarity.

Structure confidence

ColabFold pLDDT: 97.56 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) 0.873

Structure A0A0H3GJE4

Pocket Pocket 1

Druggability (FPocket) 0.217

Structure A0A0H3GJE4

Pocket Pocket 16

ColabFold model

P2Rank 0.843 · Pocket 1

FPocket 0.332 · Pocket 4

Core conservation Conserved core gene

Roary core

CoreCruncher core

Gut microbiome 229 / 4744 genomes with a hit

Prevalence 4.8%

Metabolic context

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

Explore metabolic network

Metabolic context: more central than 95.9% of genes in this genome, no human homolog detected.

Relative network centrality 95.9% more central than 95.9% of genes in this genome

Chokepoint Not a chokepoint

Imported from KpATCC43816.sbml · 2026-07-09

Sequence

Primary amino-acid sequence viewer.

MAALVELLKNPPAGEEEFLLDLLINRVPPGVDEAAYVKAGFLAAIAKGEATSPLVTPEKAVELLGTMQGGYNIHPLIDALDDAKLAPIAAKALSHTLLMFDNFYDVEEKAKAGNEHAKQVMQSWADAEWFLNRPQLAEKITVTVFKVTGETNTDDLSPAPDAWSRPDIPLHALAMLKNPREGIEPDQPGVVGPIKQIEALQQKGYPLAYVGDVVGTGSSRKSATNSVLWFMGDDIPNVPNKRGGGLCLGGKIAPIFFNTMEDAGALPIEVDVSNLNMGDVIDVYPFKGEVRNHETNELLASFELKTDVLIDEVRAGGRIPLIIGRGLTTKAREALGLPHSDVFRQAKDVAESTRGFSLAQKMVGRACGVAGIRPGAYCEPKMTSVGSQDTTGPMTRDELKDLACLGFSADLVMQSFCHTAAYPKPVDVTTHHTLPDFIMNRGGVSLRPGDGVIHSWLNRMLLPDTVGTGGDSHTRFPIGISFPAGSGLVAFAAATGVMPLDMPESVLVRFKGKMQPGITLRDLVHAIPLYAIKQGLLTVEKKGKKNIFSGRILEIEGLPDLKVEQAFELTDASAERSAAGCTIKLNKEPIVEYLNSNIVLLKWMIAEGYGDRRTLERRIQGMEKWLADPQLLEADADAEYAAVIDIDLADIKEPILCAPNDPDDARLLSDVQGEKIDEVFIGSCMTNIGHFRAAGKLLDSHKGQLPTRLWVAPPTRMDAAQLTEEGYYSVFGKSGARIEIPGCSLCMGNQARVADGATVVSTSTRNFPNRLGTGANVYLASAELAAVASLLGKLPTPEEYQTFVAQVDKTAEDTYRYLNFNQLDQYTEKADGVIFQTAV

Functional annotations

Enzyme classification and Gene Ontology terms linked to this protein.

2 EC 8 GO

Subcellular localization

Localization: Cytoplasmic

Enzyme Commission (EC)

Gene Ontology (GO)

GO:0006099 A nearly universal metabolic pathway in which the acetyl group of acetyl coenzyme A is effectively oxidized to two CO2 and four pairs of electrons are transferred to coenzymes. The acetyl group combines with oxaloacetate to form citrate, which undergoes successive transformations to isocitrate, 2-oxoglutarate, succinyl-CoA, succinate, fumarate, malate, and oxaloacetate again, thus completing the cycle. In eukaryotes the tricarboxylic acid is confined to the mitochondria. See also glyoxylate cycle.
GO:0051539 Binding to a 4 iron, 4 sulfur (4Fe-4S) cluster; this cluster consists of four iron atoms, with the inorganic sulfur atoms found between the irons and acting as bridging ligands.
GO:0003994 Catalysis of the reaction: citrate = isocitrate. The reaction occurs in two steps: (1) citrate = cis-aconitate + H2O, (2) cis-aconitate + H2O = isocitrate. This reaction is the interconversion of citrate and isocitrate via the labile, enzyme-bound intermediate cis-aconitate. Water is removed from one part of the citrate molecule and added back to a different atom to form isocitrate.
GO:0005829 The part of the cytoplasm that does not contain organelles but which does contain other particulate matter, such as protein complexes.
GO:0047456 Catalysis of the reaction: (2S,3R)-3-hydroxybutane-1,2,3-tricarboxylate = cis-2-methylaconitate + H2O.
GO:0046872 Binding to a metal ion.
GO:0003730 Binding to a 3' untranslated region of an mRNA molecule.
GO:0019629 OBSOLETE. The chemical reactions and pathways resulting in the breakdown of propionate that occurs in the 2-methylcitrate cycle.

Sequence domains and features

Domain and signature matches imported from InterPro and related databases.

38 records

Show feature table

Start	End	DB	Term	Name
358	794	CDD	cd01581	AcnB
676	693	ProSitePatterns	PS00450	Aconitase family signature 1.
676	693	InterPro	IPR018136	Aconitase family, 4Fe-4S cluster binding site
356	655	Gene3D	G3DSA:3.40.1060.10	Aconitase, Domain 2
356	655	InterPro	IPR015932	Aconitase, domain 2
145	285	CDD	cd01576	AcnB_Swivel
145	285	InterPro	IPR015929	Aconitase B, swivel
1	135	Gene3D	G3DSA:1.25.40.310	-
1	135	InterPro	IPR036288	Aconitase B, HEAT-like domain superfamily
376	503	FunFam	G3DSA:3.30.499.10:FF:000001	Aconitate hydratase B
136	345	SUPERFAMILY	SSF52016	LeuD/IlvD-like
657	839	FunFam	G3DSA:3.30.499.10:FF:000008	Aconitate hydratase B
353	833	SUPERFAMILY	SSF53732	Aconitase iron-sulfur domain
353	833	InterPro	IPR036008	Aconitase, iron-sulfur domain
657	839	Gene3D	G3DSA:3.30.499.10	Aconitase, domain 3
657	839	InterPro	IPR015931	Aconitase/3-isopropylmalate dehydratase large subunit, alpha/beta/alpha, subdomain 1/3
2	130	Pfam	PF11791	Aconitate B N-terminal domain
2	130	InterPro	IPR015933	Aconitase B, HEAT-like domain
2	134	SUPERFAMILY	SSF74778	Aconitase B, N-terminal domain
2	134	InterPro	IPR036288	Aconitase B, HEAT-like domain superfamily
446	792	Pfam	PF00330	Aconitase family (aconitate hydratase)
446	792	InterPro	IPR001030	Aconitase/3-isopropylmalate dehydratase large subunit, alpha/beta/alpha domain
136	335	FunFam	G3DSA:3.20.19.10:FF:000004	Aconitate hydratase B
488	655	FunFam	G3DSA:3.40.1060.10:FF:000002	Aconitate hydratase B
376	503	Gene3D	G3DSA:3.30.499.10	Aconitase, domain 3
376	503	InterPro	IPR015931	Aconitase/3-isopropylmalate dehydratase large subunit, alpha/beta/alpha, subdomain 1/3
136	335	Gene3D	G3DSA:3.20.19.10	Aconitase, domain 4
136	335	InterPro	IPR015928	Aconitase/3-isopropylmalate dehydratase, swivel
735	748	ProSitePatterns	PS01244	Aconitase family signature 2.
735	748	InterPro	IPR018136	Aconitase family, 4Fe-4S cluster binding site
1	833	PIRSF	PIRSF036687	AcnB
1	833	InterPro	IPR004406	Aconitase B
1	135	FunFam	G3DSA:1.25.40.310:FF:000001	Aconitate hydratase B
142	356	Pfam	PF06434	Aconitate hydratase 2 N-terminus
142	356	InterPro	IPR015929	Aconitase B, swivel
1	828	NCBIfam	TIGR00117	bifunctional aconitate hydratase 2/2-methylisocitrate dehydratase
1	828	InterPro	IPR004406	Aconitase B
219	800	PANTHER	PTHR43160	ACONITATE HYDRATASE B

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

0.873

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Surrounding area

Pocket 2 P2Rank #2

0.685

Likely same site as FPocket 16 1.6 Å 23 shared residues 92% of smaller site

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Surrounding area

Pocket 3 P2Rank #3

0.492

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Surrounding area

Pocket 4 P2Rank #4

0.441

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Surrounding area

Pocket 5 P2Rank #5

0.227

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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 #16

0.217 Unusual size

Likely same site as P2Rank 2 1.6 Å 23 shared residues 92% of smaller site

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Surrounding area

Residue sets

UniProt: Binding site:165-165

UniProt: Binding site:218-220

UniProt: Binding site:388-390

UniProt: Binding site:472-472

UniProt: Binding site:684-684

UniProt: Binding site:743-743

UniProt: Binding site:746-746

UniProt: Binding site:765-765

UniProt: Binding site:770-770

Binding pockets · P2Rank

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

Pocket 1 P2Rank #1

0.843

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Surrounding area

Pocket 2 P2Rank #2

0.558

Likely same site as FPocket 20 4.0 Å 24 shared residues 100% of smaller site

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Surrounding area

Pocket 3 P2Rank #3

0.501

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Surrounding area

Pocket 4 P2Rank #4

0.432

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Surrounding area

Pocket 5 P2Rank #5

0.353

Likely same site as FPocket 4 2.1 Å 15 shared residues 83% of smaller site

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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 #4

0.332 Unusual size

Likely same site as P2Rank 5 2.1 Å 15 shared residues 83% of smaller site

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Surrounding area

Pocket 2 FPocket #20

0.221 Unusual size

Likely same site as P2Rank 2 4.0 Å 24 shared residues 100% of smaller site

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Surrounding area

Residue sets

UniProt: Binding site:165-165

UniProt: Binding site:218-220

UniProt: Binding site:388-390

UniProt: Binding site:472-472

UniProt: Binding site:684-684

UniProt: Binding site:743-743

UniProt: Binding site:746-746

UniProt: Binding site:765-765

UniProt: Binding site:770-770

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_A0A0H3GJE4	AlphaFold DB	—	—	full sequence	—	Viewing
ColabFold VK055_2445	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.

25 records

Chemistry signal

Structural ligand evidence is available for this target.

Direct evidence 0 same-protein records

Transferred evidence 11 records from similar proteins

Structural ligands 11 0 loaded crystals

Measured bioactivity 0 direct and transferred ChEMBL records

Proposed compounds 14 similarity-based ZINC candidates

Best available ligand signal

ATH PDB via homolog 187.1 Da · LogP -5.48 · TPSA 140.6 Open detail RCSB PDB

F3S PDB via homolog Detail RCSB PDB

FLC PDB via homolog Detail RCSB PDB

ICT PDB via homolog Detail RCSB PDB

KP1 PDB via homolog Detail RCSB PDB

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
ATH RCSB PDB	1FGH	P20004	187.1 Da LogP -5.48 TPSA 140.6	✓ Ro5	✓ Clean	`C(=C(/[C@H](C(=O)[O-])O)\C(=O)[O-])/C(=O)[O-]`
F3S RCSB PDB	1L5J	P36683	295.8 Da LogP 2.59 TPSA 0.0	✓ Ro5	✓ Clean	`S1[Fe]2S[Fe]3[S]2[Fe]1S3`
FLC RCSB PDB	1B0K	P16276	189.1 Da LogP -5.25 TPSA 140.6	✓ Ro5	✓ Clean	`C(C(=O)[O-])C(CC(=O)[O-])(C(=O)[O-])O`
ICT RCSB PDB	1B0J	P16276	192.1 Da LogP -1.39 TPSA 132.1	✓ Ro5	✓ Clean	`C([C@@H]([C@H](C(=O)O)O)C(=O)O)C(=O)O`
KP1 RCSB PDB	4KP1	P81291	132.2 Da LogP 0.92 TPSA 40.5	✓ Ro5	✓ Clean	`CC(C)(CC(C)(C)O)O`
MIC RCSB PDB	1AMI	P20004	206.2 Da LogP -1.00 TPSA 132.1	✓ Ro5	✓ Clean	`C[C@@]([C@H](CC(=O)O)C(=O)O)(C(=O)O)O`
NIC RCSB PDB	8ACN	P20004	193.1 Da LogP -1.45 TPSA 138.0	✓ Ro5	✓ Clean	`C([C@@H]([C@H](C(=O)O)O)[N+](=O)[O-])C(=O)O`
NTC RCSB PDB	1NIS	P20004	193.1 Da LogP -1.45 TPSA 138.0	✓ Ro5	✓ Clean	`C(C(=O)O)[C@@](C[N+](=O)[O-])(C(=O)O)O`
O RCSB PDB	1B0K	P16276	18.0 Da LogP -0.82 TPSA 31.5	✓ Ro5	✓ Clean	`O`
TRA RCSB PDB	1L5J	P36683	171.1 Da LogP -4.45 TPSA 120.4	✓ Ro5	✓ Clean	`C(/C(=C\C(=O)[O-])/C(=O)[O-])C(=O)[O-]`
TRC RCSB PDB	5ACN	P16276	176.1 Da LogP -0.36 TPSA 111.9	✓ Ro5	✓ Clean	`C(C(CC(=O)O)C(=O)O)C(=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
ZINC1577651 ZINC	0.684	234.2 Da LogP -0.66 TPSA 149.2	✓ Ro5	✓ Clean	`O=C(O)C[C@H](C(=O)O)[C@@H](CC(=O)O)C(=O)O`
ZINC1577652 ZINC	0.684	234.2 Da LogP -0.66 TPSA 149.2	✓ Ro5	✓ Clean	`O=C(O)C[C@@H](C(=O)O)[C@@H](CC(=O)O)C(=O)O`
ZINC1577653 ZINC	0.684	234.2 Da LogP -0.66 TPSA 149.2	✓ Ro5	✓ Clean	`O=C(O)C[C@H](C(=O)O)[C@H](CC(=O)O)C(=O)O`
ZINC1623550 ZINC	0.529	240.1 Da LogP 2.00 TPSA 40.5	✓ Ro5	✓ Clean	`CC(C)(O)CC(O)(C(F)(F)F)C(F)(F)F`
ZINC45068939 ZINC	0.519	252.2 Da LogP 1.14 TPSA 111.9	✓ Ro5	✓ Clean	`O=C(O)C[C@H](CC(=O)c1ccc(O)cc1)C(=O)O`
ZINC45068942 ZINC	0.519	252.2 Da LogP 1.14 TPSA 111.9	✓ Ro5	✓ Clean	`O=C(O)C[C@@H](CC(=O)c1ccc(O)cc1)C(=O)O`
ZINC168333116 ZINC	0.515	225.2 Da LogP 0.32 TPSA 100.7	✓ Ro5	✓ Clean	`O=C(O)[C@@H](O)[C@H](Cc1ccccc1)[N+](=O)[O-]`
ZINC168342027 ZINC	0.515	225.2 Da LogP 0.32 TPSA 100.7	✓ Ro5	✓ Clean	`O=C(O)[C@H](O)[C@H](Cc1ccccc1)[N+](=O)[O-]`
ZINC33992595 ZINC	0.515	225.2 Da LogP 0.32 TPSA 100.7	✓ Ro5	✓ Clean	`O=C(O)[C@@H](O)[C@@H](Cc1ccccc1)[N+](=O)[O-]`
ZINC34050089 ZINC	0.515	225.2 Da LogP 0.32 TPSA 100.7	✓ Ro5	✓ Clean	`O=C(O)[C@H](O)[C@@H](Cc1ccccc1)[N+](=O)[O-]`
ZINC1532902 ZINC	0.500	206.2 Da LogP -0.86 TPSA 132.1	✓ Ro5	✓ Clean	`O=C(O)CC[C@@](O)(CC(=O)O)C(=O)O`
ZINC2018106 ZINC	0.500	206.2 Da LogP -0.86 TPSA 132.1	✓ Ro5	✓ Clean	`O=C(O)CC[C@](O)(CC(=O)O)C(=O)O`
ZINC4212247 ZINC	0.500	292.1 Da LogP -1.16 TPSA 189.7	1 viol.	✓ Clean	`O=C(O)C[C@@H](C(=O)O)C(P(=O)(O)O)P(=O)(O)O`
ZINC5131772 ZINC	0.500	292.1 Da LogP -1.16 TPSA 189.7	1 viol.	✓ Clean	`O=C(O)C[C@H](C(=O)O)C(P(=O)(O)O)P(=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.

Cross-references

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

Sequence

UniProt A0A0H3GJE4

Pathways

KEGG R04425 BioCyc 4.2.1.99-RXN KEGG R01900 BioCyc ACONITATEHYDR-RXN KEGG R01325 BioCyc ACONITATEDEHYDR-RXN KEGG R01324 BioCyc RXN-14047