Target Pathogen

Overview

Basic information about this protein and its source genome.

Accession: PA3121
Assembly: Pseudomonas aeruginosa PAO1, complete genome
Gene: PA3121 leuC
Status: annotated
Amino acids: 474
Structure source: AlphaFold

EC

4.2.1.33

GO

GO:0003861 Catalysis of the reaction: (2R,3S)-3-isopropylmalate = (2S)-2-isopropylmalate. 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:0046872 Binding to a metal ion. GO:0009098 The chemical reactions and pathways resulting in the formation of L-leucine, 2-amino-4-methylpentanoic acid.

Target profile

Computed evidence for target prioritization.

Human off-target: hit
Human identity (%): 32.237
Human E-value: 1.29e-09
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 0.566

Structure –

Pocket –

Sequence

Primary amino-acid sequence viewer.

Functional Annotations

Enzyme classification and Gene Ontology terms linked to this protein.

1 EC 4 GO

Enzyme Commission (EC)

1

4.2.1.33

Gene Ontology (GO)

4

GO:0003861 Catalysis of the reaction: (2R,3S)-3-isopropylmalate = (2S)-2-isopropylmalate.
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:0046872 Binding to a metal ion.
GO:0009098 The chemical reactions and pathways resulting in the formation of L-leucine, 2-amino-4-methylpentanoic acid.

Sequence Features

Domain/signature hits from InterPro and related databases.

38 records

Show feature table

Start	End	DB	Term	Name
5	292	Gene3D	G3DSA:3.30.499.10	Aconitase, domain 3
5	292	InterPro	IPR015931	Aconitase/3-isopropylmalate dehydratase large subunit, alpha/beta/alpha, subdomain 1/3
406	419	ProSitePatterns	PS01244	Aconitase family signature 2.
406	419	InterPro	IPR018136	Aconitase family, 4Fe-4S cluster binding site
139	154	PRINTS	PR00415	Aconitase family signature
139	154	InterPro	IPR001030	Aconitase/3-isopropylmalate dehydratase large subunit, alpha/beta/alpha domain
292	306	PRINTS	PR00415	Aconitase family signature
292	306	InterPro	IPR001030	Aconitase/3-isopropylmalate dehydratase large subunit, alpha/beta/alpha domain
114	122	PRINTS	PR00415	Aconitase family signature
114	122	InterPro	IPR001030	Aconitase/3-isopropylmalate dehydratase large subunit, alpha/beta/alpha domain
125	138	PRINTS	PR00415	Aconitase family signature
125	138	InterPro	IPR001030	Aconitase/3-isopropylmalate dehydratase large subunit, alpha/beta/alpha domain
201	214	PRINTS	PR00415	Aconitase family signature
201	214	InterPro	IPR001030	Aconitase/3-isopropylmalate dehydratase large subunit, alpha/beta/alpha domain
349	360	PRINTS	PR00415	Aconitase family signature
349	360	InterPro	IPR001030	Aconitase/3-isopropylmalate dehydratase large subunit, alpha/beta/alpha domain
406	419	PRINTS	PR00415	Aconitase family signature
406	419	InterPro	IPR001030	Aconitase/3-isopropylmalate dehydratase large subunit, alpha/beta/alpha domain
215	228	PRINTS	PR00415	Aconitase family signature
215	228	InterPro	IPR001030	Aconitase/3-isopropylmalate dehydratase large subunit, alpha/beta/alpha domain
88	101	PRINTS	PR00415	Aconitase family signature
88	101	InterPro	IPR001030	Aconitase/3-isopropylmalate dehydratase large subunit, alpha/beta/alpha domain
2	472	SUPERFAMILY	SSF53732	Aconitase iron-sulfur domain
2	472	InterPro	IPR036008	Aconitase, iron-sulfur domain
3	473	PANTHER	PTHR43822	HOMOACONITASE, MITOCHONDRIAL-RELATED
30	466	CDD	cd01583	IPMI
30	466	InterPro	IPR033941	3-Isopropylmalate dehydratase, catalytic domain
333	473	FunFam	G3DSA:3.30.499.10:FF:000007	3-isopropylmalate dehydratase large subunit
332	474	Gene3D	G3DSA:3.30.499.10	Aconitase, domain 3
332	474	InterPro	IPR015931	Aconitase/3-isopropylmalate dehydratase large subunit, alpha/beta/alpha, subdomain 1/3
2	473	Hamap	MF_01026	3-isopropylmalate dehydratase large subunit [leuC].
2	473	InterPro	IPR004430	3-isopropylmalate dehydratase, large subunit
345	361	ProSitePatterns	PS00450	Aconitase family signature 1.
345	361	InterPro	IPR018136	Aconitase family, 4Fe-4S cluster binding site
8	464	Pfam	PF00330	Aconitase family (aconitate hydratase)
8	464	InterPro	IPR001030	Aconitase/3-isopropylmalate dehydratase large subunit, alpha/beta/alpha domain
3	472	NCBIfam	TIGR00170	3-isopropylmalate dehydratase large subunit
3	472	InterPro	IPR004430	3-isopropylmalate dehydratase, large subunit

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

0 + 1

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

Entry	Method	Resolution	Chain	Coverage	Links	Status
AlphaFold PA3121	AlphaFold	—	—	full sequence	—	Viewing

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				0.566
4				0.252

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

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
ATH	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	5ACN	P16276	295.8 Da LogP 2.59 TPSA 0.0	✓ Ro5	✓ Clean	`S1[Fe]2S[Fe]3[S]2[Fe]1S3`
FLC	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	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	4KP1	P81291	132.2 Da LogP 0.92 TPSA 40.5	✓ Ro5	✓ Clean	`CC(C)(CC(C)(C)O)O`
MIC	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	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	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	1B0K	P16276	18.0 Da LogP -0.82 TPSA 31.5	✓ Ro5	✓ Clean	`O`
TRA	1ACO	P20004	171.1 Da LogP -4.45 TPSA 120.4	✓ Ro5	✓ Clean	`C(/C(=C\C(=O)[O-])/C(=O)[O-])C(=O)[O-]`
TRC	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	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	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	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	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	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	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	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	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	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	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	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	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	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	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.

PA3121