Protein profile

PA4694

ketol-acid reductoisomerase

Genome: NC_002516.2

Gene: PA4694 ilvC Structure source: Experimental + AlphaFold UniProt Q9HVA2

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Amino acids 338

Annotations 9

Features 25

PDB binders 11

Druggability 0.605

Overview

Basic information about this protein and its source genome.

Accession: PA4694
Assembly: Pseudomonas aeruginosa PAO1, complete genome
Gene: PA4694 ilvC
Status: annotated
Amino acids: 338
Structure source: Experimental + AlphaFold

1.1.1.86

GO:0005829 The part of the cytoplasm that does not contain organelles but which does contain other particulate matter, such as protein complexes. GO:0004455 Catalysis of the reaction: (R)-2,3-dihydroxy-3-methylbutanoate + NADP+ = (S)-2-hydroxy-2-methyl-3-oxobutanoate + NADPH + H+. GO:0000287 Binding to a magnesium (Mg) ion. GO:0050661 Binding to nicotinamide-adenine dinucleotide phosphate, a coenzyme involved in many redox and biosynthetic reactions; binding may be to either the oxidized form, NADP+, or the reduced form, NADPH. 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.

Target profile

Computed evidence for target prioritization.

Human off-target: No hit
Gut microbiome off-target: hit
Essential (DEG): Y
Localization: Cytoplasmic

Selected Druggability evidence

Selected Druggability is the FPocket score chosen for ranking using the curated structure priority. The 3D viewer may show a different loaded structure, so its visible pockets can differ.

FPocket 0.605

Structure –

Pocket –

Sequence

Primary amino-acid sequence viewer.

Functional Annotations

Enzyme classification and Gene Ontology terms linked to this protein.

1 EC 8 GO

Enzyme Commission (EC)

1.1.1.86

Gene Ontology (GO)

GO:0005829 The part of the cytoplasm that does not contain organelles but which does contain other particulate matter, such as protein complexes.
GO:0004455 Catalysis of the reaction: (R)-2,3-dihydroxy-3-methylbutanoate + NADP+ = (S)-2-hydroxy-2-methyl-3-oxobutanoate + NADPH + H+.
GO:0000287 Binding to a magnesium (Mg) ion.
GO:0050661 Binding to nicotinamide-adenine dinucleotide phosphate, a coenzyme involved in many redox and biosynthetic reactions; binding may be to either the oxidized form, NADP+, or the reduced form, NADPH.
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.
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.

Sequence Features

Domain/signature hits from InterPro and related databases.

25 records

Show feature table

Start	End	DB	Term	Name
1	328	Hamap	MF_00435	Ketol-acid reductoisomerase (NADP(+)) [ilvC].
1	328	InterPro	IPR013023	Ketol-acid reductoisomerase
182	327	ProSiteProfiles	PS51851	KARI C-terminal domain profile.
182	327	InterPro	IPR000506	Ketol-acid reductoisomerase, C-terminal
14	326	NCBIfam	TIGR00465	ketol-acid reductoisomerase
14	326	InterPro	IPR013023	Ketol-acid reductoisomerase
1	181	ProSiteProfiles	PS51850	KARI N-terminal domain profile.
1	181	InterPro	IPR013116	Ketol-acid reductoisomerase, N-terminal
183	326	Pfam	PF01450	Acetohydroxy acid isomeroreductase, catalytic domain
183	326	InterPro	IPR000506	Ketol-acid reductoisomerase, C-terminal
2	203	PIRSF	PIRSF000116	IlvC_gammaproteo
2	203	InterPro	IPR014359	Ketol-acid reductoisomerase, prokaryotic
201	332	PIRSF	PIRSF000116	IlvC_gammaproteo
201	332	InterPro	IPR014359	Ketol-acid reductoisomerase, prokaryotic
14	177	Pfam	PF07991	Acetohydroxy acid isomeroreductase, NADPH-binding domain
14	177	InterPro	IPR013116	Ketol-acid reductoisomerase, N-terminal
183	332	SUPERFAMILY	SSF48179	6-phosphogluconate dehydrogenase C-terminal domain-like
183	332	InterPro	IPR008927	6-phosphogluconate dehydrogenase-like, C-terminal domain superfamily
1	181	Gene3D	G3DSA:3.40.50.720	-
1	181	FunFam	G3DSA:3.40.50.720:FF:000023	Ketol-acid reductoisomerase (NADP(+))
1	182	SUPERFAMILY	SSF51735	NAD(P)-binding Rossmann-fold domains
1	182	InterPro	IPR036291	NAD(P)-binding domain superfamily
182	338	Gene3D	G3DSA:6.10.240.10	-
15	330	PANTHER	PTHR21371	KETOL-ACID REDUCTOISOMERASE, MITOCHONDRIAL
15	330	InterPro	IPR013023	Ketol-acid reductoisomerase

3D Structure

Selected loaded structure. Experimental PDB entries may cover only a portion of the sequence; predicted models typically cover the full protein.

Loading 3D structure...

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Structural evidence

1 + 1

Experimental PDB entries and predicted models. Click Switch to display a different structure in the viewer.

Entry	Method	Resolution	Chain	Coverage	Links	Status
PDB 1NP3	X-ray	2.00 Å	A,B,C,D	100.0% 1-338	PDBe RCSB PDBj File	Viewing
AlphaFold PA4694	AlphaFold	—	—	full sequence	—	Loaded

Pocket details FPocket · P2Rank — toggle visibility and zoom from here, or open full viewer

Pockets (FPOCKET)

Showing top-ranked FPocket candidates by druggability. Druggability is color-coded: high (0.7 or higher), medium (0.4 to 0.69), low (below 0.4).

FPOCKET	Sticks	Spheres	Surfaces	Druggability	Labels	Zoom	Positions
2				0.605

Pockets (P2RANK)

Showing top-ranked P2Rank candidates by probability. Probability is color-coded per P2Rank calibration: high (≥ 0.5), medium (0.2 – 0.49), low (< 0.2).

P2RANK	Sticks	Spheres	Surfaces	Score	Probability	Labels	Zoom	Positions
1				5.45	0.259

Pockets (FPOCKET)

Showing top-ranked FPocket candidates by druggability. Druggability is color-coded: high (0.7 or higher), medium (0.4 to 0.69), low (below 0.4).

FPOCKET	Sticks	Spheres	Surfaces	Druggability	Labels	Zoom	Positions
1				0.65
3				0.625
5				0.456

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.

61 records

Highest-confidence structural evidence: ligands co-crystallized with this exact protein. If the source PDB is loaded in TPW, 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	6AQJ	Q2YUF3	131.1 Da LogP -0.40 TPSA 66.4	✓ Ro5	✓ Clean	`CC(C)NC(=O)C(=O)O`
81B	6C5N	Q2YUF3	157.2 Da LogP 0.13 TPSA 66.4	✓ Ro5	✓ Clean	`C1CCC(C1)NC(=O)C(=O)O`
9TY	5W3K	Q2FWK4	130.1 Da LogP -0.06 TPSA 74.6	✓ Ro5	✓ Clean	`C1CC1(C(=O)O)C(=O)O`
E9G	6BUL	Q2YUF3	209.2 Da LogP 1.05 TPSA 77.8	✓ Ro5	✓ Clean	`C[C@@H](c1ccccc1)N(C(=O)C(=O)O)O`
EKA	6C55	Q2YUF3	187.2 Da LogP 0.62 TPSA 77.8	✓ Ro5	✓ Clean	`C1CCC(CC1)N(C(=O)C(=O)O)O`
EKD	6C55	Q2YUF3	171.2 Da LogP 0.52 TPSA 66.4	✓ Ro5	✓ Clean	`C1CCC(CC1)NC(=O)C(=O)O`
EN4	6C5N	Q2YUF3	173.2 Da LogP 0.23 TPSA 77.8	✓ Ro5	✓ Clean	`C1CCC(C1)N(C(=O)C(=O)O)O`
HIO	4KQX	D0WGK0	147.1 Da LogP -0.30 TPSA 77.8	✓ Ro5	✓ Clean	`CC(C)N(C(=O)C(=O)O)O`
NH4	6L2Z	Q04M32	18.0 Da LogP 0.38 TPSA 36.5	✓ Ro5	✓ Clean	`[NH4+]`
R67	6VO2	Q2FWK4	166.2 Da LogP -1.32 TPSA 88.5	✓ Ro5	✓ Clean	`CS(=O)(=O)CC(=O)C(=O)O`
TLA	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
ZINC1555430	0.714	252.4 Da LogP 1.88 TPSA 58.2	✓ Ro5	✓ Clean	`O=C(NC1CCCCC1)C(=O)NC1CCCCC1`
ZINC2990143	0.714	266.4 Da LogP 2.27 TPSA 58.2	✓ Ro5	✓ Clean	`O=C(NC1CCCCCC1)C(=O)NC1CCCCC1`
ZINC2991980	0.714	252.4 Da LogP 1.88 TPSA 58.2	✓ Ro5	✓ Clean	`O=C(NC1CCCCCC1)C(=O)NC1CCCC1`
ZINC3093187	0.714	238.3 Da LogP 1.49 TPSA 58.2	✓ Ro5	✓ Clean	`O=C(NC1CCCCC1)C(=O)NC1CCCC1`
ZINC5494839	0.714	280.4 Da LogP 2.66 TPSA 58.2	✓ Ro5	✓ Clean	`O=C(NC1CCCCCC1)C(=O)NC1CCCCCC1`
ZINC12359024	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	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	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	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	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	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	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	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	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`
ZINC2810428	0.682	210.3 Da LogP 0.71 TPSA 58.2	✓ Ro5	✓ Clean	`O=C(NC1CCCCC1)C(=O)NC1CC1`
ZINC4856283	0.682	224.3 Da LogP 1.10 TPSA 58.2	✓ Ro5	✓ Clean	`O=C(NC1CCCCCC1)C(=O)NC1CC1`
ZINC31729329	0.632	240.3 Da LogP 2.67 TPSA 74.6	✓ Ro5	✓ Clean	`O=C(O)C1(C(=O)O)CCC2(CCCCC2)CC1`
ZINC4826010	0.600	282.5 Da LogP 3.08 TPSA 41.1	✓ Ro5	✓ Clean	`O=C(NC1CCCCCC1)C(=S)NC1CCCCC1`
ZINC4828575	0.600	268.4 Da LogP 2.69 TPSA 41.1	✓ Ro5	✓ Clean	`O=C(NC1CCCCCC1)C(=S)NC1CCCC1`
ZINC5188775	0.600	268.4 Da LogP 2.69 TPSA 41.1	✓ Ro5	✓ Clean	`O=C(NC1CCCCC1)C(=S)NC1CCCCC1`
ZINC5282724	0.600	232.1 Da LogP -0.91 TPSA 149.2	✓ Ro5	✓ Clean	`O=C(O)C1(C(=O)O)CC(C(=O)O)(C(=O)O)C1`
ZINC6690924	0.600	254.4 Da LogP 2.29 TPSA 41.1	✓ Ro5	✓ Clean	`O=C(NC1CCCCC1)C(=S)NC1CCCC1`
ZINC1560405156	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	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`
ZINC157375	0.565	224.3 Da LogP 2.95 TPSA 41.1	✓ Ro5	✓ Clean	`O=C(NC1CCCCC1)NC1CCCCC1`
ZINC370205	0.565	252.4 Da LogP 3.73 TPSA 41.1	✓ Ro5	✓ Clean	`O=C(NC1CCCCCCC1)NC1CCCCC1`
ZINC376044	0.565	238.4 Da LogP 3.34 TPSA 41.1	✓ Ro5	✓ Clean	`O=C(NC1CCCCCC1)NC1CCCCC1`
ZINC44123745	0.565	252.4 Da LogP 3.73 TPSA 41.1	✓ Ro5	✓ Clean	`O=C(NC1CCCCCC1)NC1CCCCCC1`
ZINC6700931	0.556	280.4 Da LogP 2.52 TPSA 58.2	✓ Ro5	✓ Clean	`CC1CCC(NC(=O)C(=O)NC2CCCCCC2)CC1`
ZINC100357297	0.542	254.4 Da LogP 2.13 TPSA 58.2	✓ Ro5	✓ Clean	`CC(=O)N[C@H]1CCCC[C@@H](NC(C)=O)CCCC1`
ZINC245239336	0.542	254.4 Da LogP 2.13 TPSA 58.2	✓ Ro5	✓ Clean	`CC(=O)N[C@H]1CCCC[C@@H](NC(C)=O)CCCC1`
ZINC48844720	0.542	210.3 Da LogP 2.56 TPSA 41.1	✓ Ro5	✓ Clean	`O=C(NC1CCCCCCC1)NC1CC1`
ZINC2325811420	0.538	362.5 Da LogP 2.05 TPSA 92.3	✓ Ro5	✓ Clean	`O=C(NC1CCC(NC(=O)C(=O)C2CCCC2)CC1)C(=O)C1CCCC1`
ZINC2988383	0.536	226.3 Da LogP 1.35 TPSA 58.2	✓ Ro5	✓ Clean	`CC(C)NC(=O)C(=O)NC1CCCCCC1`
ZINC5068665	0.536	210.3 Da LogP 0.67 TPSA 49.4	✓ Ro5	✓ Clean	`O=C(NC1CCCC1)C(=O)N1CCCC1`
ZINC244257594	0.520	294.4 Da LogP 3.05 TPSA 58.2	✓ Ro5	✓ Clean	`O=C(CC(=O)NC1CCCCCC1)NC1CCCCCC1`
ZINC2747187	0.520	252.4 Da LogP 1.88 TPSA 58.2	✓ Ro5	✓ Clean	`O=C(CCC(=O)NC1CCCC1)NC1CCCC1`
ZINC3157376	0.520	266.4 Da LogP 2.27 TPSA 58.2	✓ Ro5	✓ Clean	`O=C(CC(=O)NC1CCCCC1)NC1CCCCC1`
ZINC358703	0.520	312.4 Da LogP 0.61 TPSA 98.7	✓ Ro5	✓ Clean	`O=C(NC1CCCCC1)[C@H](O)[C@@H](O)C(=O)NC1CCCCC1`
ZINC253419731	0.517	211.3 Da LogP 1.76 TPSA 49.3	✓ Ro5	✓ Clean	`C=C(CO)C(=O)NC1CCCCCCC1`
ZINC2989882	0.517	252.4 Da LogP 1.84 TPSA 49.4	✓ Ro5	✓ Clean	`O=C(NC1CCCCCC1)C(=O)N1CCCCC1`
ZINC4694330	0.517	224.3 Da LogP 1.06 TPSA 49.4	✓ Ro5	✓ Clean	`O=C(NC1CCCCC1)C(=O)N1CCCC1`
ZINC242273691	0.516	216.2 Da LogP -1.36 TPSA 89.9	✓ Ro5	✓ Clean	`O=C(O)C(=O)NC1CCN(CCO)CC1`
ZINC2959530	0.516	232.3 Da LogP 1.68 TPSA 58.2	✓ Ro5	✓ Clean	`O=C(Nc1ccccc1)C(=O)NC1CCCC1`
ZINC83889467	0.516	226.3 Da LogP 0.06 TPSA 69.6	✓ Ro5	✓ Clean	`O=C(O)C(=O)NC1CCN(CC2CC2)CC1`
ZINC1529331	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	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	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	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`
ZINC461598	0.500	239.3 Da LogP 1.94 TPSA 66.4	✓ Ro5	✓ Clean	`O=C(O)[C@H]1CCCC[C@@H]1C(=O)NC1CCCC1`

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.