KpATCC43816 Protein target profile

ketol-acid reductoisomerase

Accession: VK055_3202

Gene: AIK81770.1 ilvC 3D evidence: AlphaFold DB model + ColabFold model Metabolism 4 reactions UniProt A0A0H3GH22

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Length 491

Pocket druggability (P2Rank · AlphaFold DB model) 0.885

Metabolic reactions 4

Chokepoint No

Direct ligand evidence 0 20 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

Central metabolic position More central than 90.7% 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. Core gene across strains Marked as conserved by both pan-genome tools: Roary and CoreCruncher. 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: 3.8% of screened genomes Lower prevalence suggests narrower overlap with the screened gut microbiome.

Essentiality

Essential (DEG): N
DEG identity (%): 39.322 Higher values support similarity to known essential genes.

Structure confidence

ColabFold pLDDT: 96.22 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) 0.885

Structure A0A0H3GH22

Pocket Pocket 1

Druggability (FPocket) 0.349

Structure A0A0H3GH22

Pocket Pocket 10

ColabFold model

P2Rank 0.924 · Pocket 1

FPocket 0.805 · Pocket 1

Core conservation Conserved core gene

Roary core

CoreCruncher core

Gut microbiome 180 / 4744 genomes with a hit

Prevalence 3.8%

Metabolic context

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

Explore metabolic network

Metabolic context: more central than 90.7% of genes in this genome, no human homolog detected.

Relative network centrality 90.7% more central than 90.7% of genes in this genome

Chokepoint Not a chokepoint

Imported from KpATCC43816.sbml · 2026-07-09

Sequence

Primary amino-acid sequence viewer.

MANYFNTLNLRQQLAQLGKCRFMARDEFADGASYLQGKKVVIVGCGAQGLNQGLNMRDSGLDISYALRKEAIAEKRASWRKATENGFKVGTYEELIPQADLVVNLTPDKQHSDVVRSVQPLMKDGAALGYSHGFNIVEVGEQIRKDITVVMVAPKCPGTEVREEYKRGFGVPTLIAVHPENDPKGEGMAIAKAWAAATGGHRAGVLESSFVAEVKSDLMGEQTILCGMLQAGSLLCFDKLVAEGTDPAYAEKLIQFGWETITEALKQGGITLMMDRLSNPAKLRAYVLSEQLKEIMAPLFQKHMDDIISGEFSSGMMADWANDDKKLLTWREETGKTAFETAPQYEGKIGEQEYFDKGVLMIAMVKAGVELAFETMVASGIIEESAYYESLHELPLIANTIARKRLYEMNVVISDTAEYGNYLFSYACVPLLKEFMTTLQTGDLGTAIAEGAVDNAQLRDVNEAIRSHAIEQVGKKLRGYMTDMKRIAVAG

Functional annotations

Enzyme classification and Gene Ontology terms linked to this protein.

1 EC 7 GO

Subcellular localization

Localization: Cytoplasmic

Enzyme Commission (EC)

1.1.1.86

Gene Ontology (GO)

GO:0004455 Catalysis of the reaction: (R)-2,3-dihydroxy-3-methylbutanoate + NADP+ = (S)-2-hydroxy-2-methyl-3-oxobutanoate + NADPH + H+.
GO:0016491 Catalysis of an oxidation-reduction (redox) reaction, a reversible chemical reaction in which the oxidation state of an atom or atoms within a molecule is altered. One substrate acts as a hydrogen or electron donor and becomes oxidized, while the other acts as hydrogen or electron acceptor and becomes reduced.
GO:0009082 The chemical reactions and pathways resulting in the formation of amino acids containing a branched carbon skeleton, comprising isoleucine, leucine and valine.
GO:0005829 The part of the cytoplasm that does not contain organelles but which does contain other particulate matter, such as protein complexes.
GO:0000287 Binding to a magnesium (Mg) ion.
GO:0009097 OBSOLETE. The chemical reactions and pathways resulting in the formation of isoleucine, (2R*,3R*)-2-amino-3-methylpentanoic acid.
GO:0009099 The chemical reactions and pathways resulting in the formation of valine, 2-amino-3-methylbutanoic acid.

Sequence domains and features

Domain and signature matches imported from InterPro and related databases.

29 records

Show feature table

Start	End	DB	Term	Name
15	208	ProSiteProfiles	PS51850	KARI N-terminal domain profile.
15	208	InterPro	IPR013116	Ketol-acid reductoisomerase, N-terminal
345	484	ProSiteProfiles	PS51851	KARI C-terminal domain profile.
345	484	InterPro	IPR000506	Ketol-acid reductoisomerase, C-terminal
22	485	Hamap	MF_00435	Ketol-acid reductoisomerase (NADP(+)) [ilvC].
22	485	InterPro	IPR013023	Ketol-acid reductoisomerase
209	491	FunFam	G3DSA:1.10.1040.10:FF:000007	Ketol-acid reductoisomerase (NADP(+))
209	491	Gene3D	G3DSA:1.10.1040.10	-
209	491	InterPro	IPR013328	6-phosphogluconate dehydrogenase, domain 2
1	334	PANTHER	PTHR21371	KETOL-ACID REDUCTOISOMERASE, MITOCHONDRIAL
1	334	InterPro	IPR013023	Ketol-acid reductoisomerase
349	484	SUPERFAMILY	SSF48179	6-phosphogluconate dehydrogenase C-terminal domain-like
349	484	InterPro	IPR008927	6-phosphogluconate dehydrogenase-like, C-terminal domain superfamily
209	344	ProSiteProfiles	PS51851	KARI C-terminal domain profile.
209	344	InterPro	IPR000506	Ketol-acid reductoisomerase, C-terminal
360	481	Pfam	PF01450	Acetohydroxy acid isomeroreductase, catalytic domain
360	481	InterPro	IPR000506	Ketol-acid reductoisomerase, C-terminal
210	342	Pfam	PF01450	Acetohydroxy acid isomeroreductase, catalytic domain
210	342	InterPro	IPR000506	Ketol-acid reductoisomerase, C-terminal
29	209	SUPERFAMILY	SSF51735	NAD(P)-binding Rossmann-fold domains
29	209	InterPro	IPR036291	NAD(P)-binding domain superfamily
1	208	Gene3D	G3DSA:3.40.50.720	-
1	208	FunFam	G3DSA:3.40.50.720:FF:000043	Ketol-acid reductoisomerase (NADP(+))
210	370	SUPERFAMILY	SSF48179	6-phosphogluconate dehydrogenase C-terminal domain-like
210	370	InterPro	IPR008927	6-phosphogluconate dehydrogenase-like, C-terminal domain superfamily
35	204	Pfam	PF07991	Acetohydroxy acid isomeroreductase, NADPH-binding domain
35	204	InterPro	IPR013116	Ketol-acid reductoisomerase, N-terminal
35	368	NCBIfam	TIGR00465	ketol-acid reductoisomerase
35	368	InterPro	IPR013023	Ketol-acid reductoisomerase

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

0.885

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Surrounding area

Pocket 2 P2Rank #2

0.531

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Surrounding area

Pocket 3 P2Rank #3

0.416

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Surrounding area

Pocket 4 P2Rank #4

0.161

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Surrounding area

Pocket 5 P2Rank #5

0.156

Likely same site as FPocket 10 2.3 Å 7 shared residues 78% 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 #10

0.349

Likely same site as P2Rank 5 2.3 Å 7 shared residues 78% of smaller site

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Surrounding area

Residue sets

UniProt: Active site:132-132

UniProt: Binding site:108-110

UniProt: Binding site:158-158

UniProt: Binding site:217-217

UniProt: Binding site:221-221

UniProt: Binding site:278-278

UniProt: Binding site:389-389

UniProt: Binding site:393-393

UniProt: Binding site:414-414

UniProt: Binding site:45-48

UniProt: Binding site:68-68

UniProt: Binding site:76-76

UniProt: Binding site:78-78

Binding pockets · P2Rank

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

Pocket 1 P2Rank #1

0.924

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Surrounding area

Pocket 2 P2Rank #2

0.617

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Surrounding area

Pocket 3 P2Rank #3

0.288

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Surrounding area

Pocket 4 P2Rank #4

0.204

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Surrounding area

Pocket 5 P2Rank #5

0.086

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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 #1

0.805

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Surrounding area

Pocket 2 FPocket #25

0.616

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Surrounding area

Pocket 3 FPocket #15

0.502

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Surrounding area

Residue sets

UniProt: Active site:132-132

UniProt: Binding site:108-110

UniProt: Binding site:158-158

UniProt: Binding site:217-217

UniProt: Binding site:221-221

UniProt: Binding site:278-278

UniProt: Binding site:389-389

UniProt: Binding site:393-393

UniProt: Binding site:414-414

UniProt: Binding site:45-48

UniProt: Binding site:68-68

UniProt: Binding site:76-76

UniProt: Binding site:78-78

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_A0A0H3GH22	AlphaFold DB	—	—	full sequence	—	Viewing
ColabFold VK055_3202	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.

20 records

Chemistry signal

Structural ligand evidence is available for this target.

Direct evidence 0 same-protein records

Transferred evidence 4 records from similar proteins

Structural ligands 4 0 loaded crystals

Measured bioactivity 0 direct and transferred ChEMBL records

Proposed compounds 16 similarity-based ZINC candidates

Best available ligand signal

40E PDB via homolog 131.1 Da · LogP -0.40 · TPSA 66.4 Open detail RCSB PDB

HIO PDB via homolog Detail RCSB PDB

NH4 PDB via homolog Detail RCSB PDB

TLA PDB via homolog Detail RCSB PDB

ZINC12359024 ZINC proposed compound · Tanimoto 0.692 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
40E RCSB PDB	4XDZ	E0SRA9	131.1 Da LogP -0.40 TPSA 66.4	✓ Ro5	✓ Clean	`CC(C)NC(=O)C(=O)O`
HIO RCSB PDB	4KQX	D0WGK0	147.1 Da LogP -0.30 TPSA 77.8	✓ Ro5	✓ Clean	`CC(C)N(C(=O)C(=O)O)O`
NH4 RCSB PDB	6L2Z	Q04M32	18.0 Da LogP 0.38 TPSA 36.5	✓ Ro5	✓ Clean	`[NH4+]`
TLA RCSB PDB	4TSK	C8WR67	150.1 Da LogP -2.12 TPSA 115.1	✓ Ro5	✓ Clean	`[C@@H]([C@H](C(=O)O)O)(C(=O)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
ZINC12359024 ZINC	0.692	210.1 Da LogP -3.40 TPSA 155.5	1 viol.	✓ Clean	`O=C(O)[C@@H](O)[C@H](O)[C@H](O)[C@@H](O)C(=O)O`
ZINC13533920 ZINC	0.692	210.1 Da LogP -3.40 TPSA 155.5	1 viol.	✓ Clean	`O=C(O)[C@@H](O)[C@H](O)[C@@H](O)[C@@H](O)C(=O)O`
ZINC1532740 ZINC	0.692	210.1 Da LogP -3.40 TPSA 155.5	1 viol.	✓ Clean	`O=C(O)[C@@H](O)[C@H](O)[C@@H](O)[C@H](O)C(=O)O`
ZINC1549593 ZINC	0.692	210.1 Da LogP -3.40 TPSA 155.5	1 viol.	✓ Clean	`O=C(O)[C@H](O)[C@H](O)[C@@H](O)[C@@H](O)C(=O)O`
ZINC2013424 ZINC	0.692	210.1 Da LogP -3.40 TPSA 155.5	1 viol.	✓ Clean	`O=C(O)[C@@H](O)[C@@H](O)[C@@H](O)[C@H](O)C(=O)O`
ZINC3581021 ZINC	0.692	210.1 Da LogP -3.40 TPSA 155.5	1 viol.	✓ Clean	`O=C(O)[C@H](O)[C@@H](O)[C@@H](O)[C@@H](O)C(=O)O`
ZINC3860635 ZINC	0.692	210.1 Da LogP -3.40 TPSA 155.5	1 viol.	✓ Clean	`O=C(O)[C@@H](O)[C@@H](O)[C@H](O)[C@H](O)C(=O)O`
ZINC5783661 ZINC	0.692	210.1 Da LogP -3.40 TPSA 155.5	1 viol.	✓ Clean	`O=C(O)[C@@H](O)[C@@H](O)[C@H](O)[C@@H](O)C(=O)O`
ZINC6072527 ZINC	0.692	210.1 Da LogP -3.40 TPSA 155.5	1 viol.	✓ Clean	`O=C(O)[C@@H](O)[C@@H](O)[C@@H](O)[C@@H](O)C(=O)O`
ZINC1560405156 ZINC	0.588	208.1 Da LogP -1.79 TPSA 155.5	1 viol.	✓ Clean	`O=C(O)/C(O)=C(\O)[C@H](O)[C@H](O)C(=O)O`
ZINC1560405157 ZINC	0.588	208.1 Da LogP -1.79 TPSA 155.5	1 viol.	✓ Clean	`O=C(O)/C(O)=C(/O)[C@H](O)[C@H](O)C(=O)O`
ZINC1529331 ZINC	0.500	206.1 Da LogP -2.21 TPSA 149.2	✓ Ro5	✓ Clean	`O=C(O)C(=O)[C@H](C(=O)O)[C@@H](O)C(=O)O`
ZINC1529332 ZINC	0.500	206.1 Da LogP -2.21 TPSA 149.2	✓ Ro5	✓ Clean	`O=C(O)C(=O)[C@H](C(=O)O)[C@H](O)C(=O)O`
ZINC1529333 ZINC	0.500	206.1 Da LogP -2.21 TPSA 149.2	✓ Ro5	✓ Clean	`O=C(O)C(=O)[C@@H](C(=O)O)[C@@H](O)C(=O)O`
ZINC1529334 ZINC	0.500	206.1 Da LogP -2.21 TPSA 149.2	✓ Ro5	✓ Clean	`O=C(O)C(=O)[C@@H](C(=O)O)[C@H](O)C(=O)O`
ZINC26577965 ZINC	0.500	203.2 Da LogP -0.31 TPSA 103.7	✓ Ro5	✓ Clean	`CC(C)C[C@@H](NC(=O)C(=O)O)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 A0A0H3GH22

Pathways

KEGG R04439 BioCyc ACETOLACTREDUCTOISOM-RXN BioCyc ACETOOHBUTREDUCTOISOM-RXN BioCyc RXN-16062-1-KETO-2-METHYLVALERATE/NAD//2-ACETO-2-HYDROXY-BUTYRATE/NADH/PROTON.68. BioCyc RXN-16061-CPD-13357/NAD//2-ACETO-LACTATE/NADH/PROTON.43.