Protein profile

PA3996

lipoyl synthase

Genome: NC_002516.2

Gene: lis Structure source: ColabFold

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Amino acids 327

Annotations 5

Features 24

PDB binders 6

Druggability 0.775

Overview

Basic information about this protein and its source genome.

Accession: PA3996
Assembly: Pseudomonas aeruginosa PAO1, complete genome
Gene: lis
Status: annotated
Amino acids: 327
Structure source: ColabFold

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:0051536 Binding to an iron-sulfur cluster, a combination of iron and sulfur atoms. GO:0009107 The chemical reactions and pathways resulting in the formation of lipoate, 1,2-dithiolane-3-pentanoate, the anion derived from lipoic acid. 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:0016992 Catalysis of the reaction: [[Fe-S] cluster scaffold protein carrying a second [4Fe-4S]2+ cluster] + N(6)-octanoyl-L-lysyl-[protein] + 2 oxidized [2Fe-2S]-[ferredoxin] + 2 S-adenosyl-L-methionine + 4 H+ = [[Fe-S] cluster scaffold protein] + N(6)-[(R)-dihydrolipoyl]-L-lysyl-[protein] + 4 Fe3+ + 2 hydrogen sulfide + 2 5'-deoxyadenosine + 2 L-methionine + 2 reduced [2Fe-2S]-[ferredoxin].

Target profile

Computed evidence for target prioritization.

Human off-target: hit
Human identity (%): 49.425
Human E-value: 1.55e-50
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 0.775

Structure –

Pocket –

Sequence

Primary amino-acid sequence viewer.

Functional Annotations

Enzyme classification and Gene Ontology terms linked to this protein.

5 GO

Gene Ontology (GO)

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:0051536 Binding to an iron-sulfur cluster, a combination of iron and sulfur atoms.
GO:0009107 The chemical reactions and pathways resulting in the formation of lipoate, 1,2-dithiolane-3-pentanoate, the anion derived from lipoic acid.
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:0016992 Catalysis of the reaction: [[Fe-S] cluster scaffold protein carrying a second [4Fe-4S]2+ cluster] + N(6)-octanoyl-L-lysyl-[protein] + 2 oxidized [2Fe-2S]-[ferredoxin] + 2 S-adenosyl-L-methionine + 4 H+ = [[Fe-S] cluster scaffold protein] + N(6)-[(R)-dihydrolipoyl]-L-lysyl-[protein] + 4 Fe3+ + 2 hydrogen sulfide + 2 5'-deoxyadenosine + 2 L-methionine + 2 reduced [2Fe-2S]-[ferredoxin].

Sequence Features

Domain/signature hits from InterPro and related databases.

24 records

Show feature table

Start	End	DB	Term	Name
6	327	PIRSF	PIRSF005963	Lipoyl_synth
6	327	InterPro	IPR003698	Lipoyl synthase
38	321	NCBIfam	TIGR00510	lipoyl synthase
38	321	InterPro	IPR003698	Lipoyl synthase
56	322	SUPERFAMILY	SSF102114	Radical SAM enzymes
87	298	FunFam	G3DSA:3.20.20.70:FF:000023	Lipoyl synthase
40	322	PANTHER	PTHR10949	LIPOYL SYNTHASE
40	322	InterPro	IPR003698	Lipoyl synthase
97	256	Pfam	PF04055	Radical SAM superfamily
97	256	InterPro	IPR007197	Radical SAM
39	324	SFLD	SFLDF00271	lipoyl synthase
39	324	InterPro	IPR003698	Lipoyl synthase
97	272	CDD	cd01335	Radical_SAM
87	307	Gene3D	G3DSA:3.20.20.70	Aldolase class I
87	307	InterPro	IPR013785	Aldolase-type TIM barrel
1	327	Hamap	MF_00206	Lipoyl synthase [lipA].
1	327	InterPro	IPR003698	Lipoyl synthase
43	79	Pfam	PF16881	N-terminal domain of lipoyl synthase of Radical_SAM family
43	79	InterPro	IPR031691	Lipoyl synthase, N-terminal
39	324	SFLD	SFLDG01058	lipoyl synthase like
90	299	SMART	SM00729	MiaB
90	299	InterPro	IPR006638	Elp3/MiaA/NifB-like, radical SAM core domain
86	303	ProSiteProfiles	PS51918	Radical SAM core domain profile.
86	303	InterPro	IPR007197	Radical SAM

3D Structure

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

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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
ColabFold PA3996	ColabFold	—	—	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
1				0.775

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.

56 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
5AD	5EXK	P9WK91	251.2 Da LogP -0.95 TPSA 119.3	✓ Ro5	✓ Clean	`C[C@@H]1[C@H]([C@H]([C@@H](O1)n2cnc3c2ncnc3N)O)O`
DTT	4U0O	Q8DLC2	154.3 Da LogP -0.43 TPSA 40.5	✓ Ro5	✓ Clean	`C([C@@H]([C@H](CS)O)O)S`
DTV	5EXI	P9WK91	154.3 Da LogP -0.43 TPSA 40.5	✓ Ro5	✓ Clean	`C([C@H]([C@@H](CS)O)O)S`
F3S	5EXK	P9WK91	295.8 Da LogP 2.59 TPSA 0.0	✓ Ro5	✓ Clean	`S1[Fe]2S[Fe]3[S]2[Fe]1S3`
MTA	4U0O	Q8DLC2	297.3 Da LogP -0.61 TPSA 119.3	✓ Ro5	✓ Clean	`CSC[C@@H]1[C@H]([C@H]([C@@H](O1)n2cnc3c2ncnc3N)…`
XOK	5EXK	P9WK91	304.5 Da LogP 1.95 TPSA 92.4	✓ Ro5	✓ Clean	`CC[C@@H](CCCCC(=O)NCCCC[C@@H](C(=O)O)N)S`

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
ZINC100349915	1.000	297.3 Da LogP -0.61 TPSA 119.3	✓ Ro5	✓ Clean	`CSC[C@@H]1O[C@H](n2cnc3c(N)ncnc32)[C@H](O)[C@@H…`
ZINC105279440	1.000	297.3 Da LogP -0.61 TPSA 119.3	✓ Ro5	✓ Clean	`CSC[C@H]1O[C@H](n2cnc3c(N)ncnc32)[C@H](O)[C@H]1O`
ZINC12501834	1.000	297.3 Da LogP -0.61 TPSA 119.3	✓ Ro5	✓ Clean	`CSC[C@@H]1O[C@H](n2cnc3c(N)ncnc32)[C@@H](O)[C@@…`
ZINC1318753	1.000	297.3 Da LogP -0.61 TPSA 119.3	✓ Ro5	✓ Clean	`CSC[C@@H]1O[C@H](n2cnc3c(N)ncnc32)[C@H](O)[C@H]…`
ZINC25963247	1.000	297.3 Da LogP -0.61 TPSA 119.3	✓ Ro5	✓ Clean	`CSC[C@H]1O[C@H](n2cnc3c(N)ncnc32)[C@@H](O)[C@H]…`
ZINC3869309	1.000	251.2 Da LogP -0.95 TPSA 119.3	✓ Ro5	✓ Clean	`C[C@H]1O[C@@H](n2cnc3c(N)ncnc32)[C@@H](O)[C@H]1O`
ZINC3869319	1.000	297.3 Da LogP -0.61 TPSA 119.3	✓ Ro5	✓ Clean	`CSC[C@H]1O[C@@H](n2cnc3c(N)ncnc32)[C@@H](O)[C@H…`
ZINC4228245	1.000	297.3 Da LogP -0.61 TPSA 119.3	✓ Ro5	✓ Clean	`CSC[C@H]1O[C@@H](n2cnc3c(N)ncnc32)[C@H](O)[C@@H…`
ZINC5929300	1.000	297.3 Da LogP -0.61 TPSA 119.3	✓ Ro5	✓ Clean	`CSC[C@H]1O[C@@H](n2cnc3c(N)ncnc32)[C@H](O)[C@H]…`
ZINC895091	1.000	297.3 Da LogP -0.61 TPSA 119.3	✓ Ro5	✓ Clean	`CSC[C@@H]1O[C@H](n2cnc3c(N)ncnc32)[C@@H](O)[C@H…`
ZINC253500647	0.766	298.3 Da LogP -0.49 TPSA 113.5	✓ Ro5	✓ Clean	`CSC[C@@H]1O[C@H](n2cnc3c(O)ncnc32)[C@H](O)[C@H]…`
ZINC5139067	0.756	283.3 Da LogP -1.04 TPSA 119.3	✓ Ro5	✓ Clean	`Nc1ncnc2c1ncn2[C@@H]1O[C@H](CS)[C@@H](O)[C@H]1O`
ZINC14766197	0.745	339.4 Da LogP 0.42 TPSA 119.3	✓ Ro5	✓ Clean	`CC(C)CSC[C@@H]1O[C@H](n2cnc3c(N)ncnc32)[C@@H](O…`
ZINC201682330	0.745	339.4 Da LogP 0.42 TPSA 119.3	✓ Ro5	✓ Clean	`CC(C)CSC[C@@H]1O[C@H](n2cnc3c(N)ncnc32)[C@H](O)…`
ZINC248157271	0.745	339.4 Da LogP 0.42 TPSA 119.3	✓ Ro5	✓ Clean	`CC(C)CSC[C@@H]1O[C@H](n2cnc3c(N)ncnc32)[C@H](O)…`
ZINC2516140	0.745	339.4 Da LogP 0.42 TPSA 119.3	✓ Ro5	✓ Clean	`CC(C)CSC[C@@H]1O[C@H](n2cnc3c(N)ncnc32)[C@@H](O…`
ZINC5138266	0.745	339.4 Da LogP 0.42 TPSA 119.3	✓ Ro5	✓ Clean	`CC(C)CSC[C@H]1O[C@@H](n2cnc3c(N)ncnc32)[C@H](O)…`
ZINC2047403	0.739	267.2 Da LogP -1.98 TPSA 139.5	✓ Ro5	✓ Clean	`Nc1ncnc2c1ncn2[C@H]1O[C@@H](CO)[C@@H](O)[C@@H]1O`
ZINC2047673	0.739	267.2 Da LogP -1.98 TPSA 139.5	✓ Ro5	✓ Clean	`Nc1ncnc2c1ncn2[C@@H]1O[C@@H](CO)[C@H](O)[C@@H]1O`
ZINC2169830	0.739	267.2 Da LogP -1.98 TPSA 139.5	✓ Ro5	✓ Clean	`Nc1ncnc2c1ncn2[C@@H]1O[C@H](CO)[C@@H](O)[C@H]1O`
ZINC3201876	0.739	267.2 Da LogP -1.98 TPSA 139.5	✓ Ro5	✓ Clean	`Nc1ncnc2c1ncn2[C@H]1O[C@H](CO)[C@@H](O)[C@@H]1O`
ZINC3201878	0.739	267.2 Da LogP -1.98 TPSA 139.5	✓ Ro5	✓ Clean	`Nc1ncnc2c1ncn2[C@@H]1O[C@@H](CO)[C@@H](O)[C@@H]…`
ZINC3814316	0.739	266.3 Da LogP -2.01 TPSA 145.3	✓ Ro5	✓ Clean	`NC[C@H]1O[C@@H](n2cnc3c(N)ncnc32)[C@H](O)[C@@H]…`
ZINC3830178	0.739	267.2 Da LogP -1.98 TPSA 139.5	✓ Ro5	✓ Clean	`Nc1ncnc2c1ncn2[C@H]1O[C@@H](CO)[C@@H](O)[C@H]1O`
ZINC3830179	0.739	267.2 Da LogP -1.98 TPSA 139.5	✓ Ro5	✓ Clean	`Nc1ncnc2c1ncn2[C@@H]1O[C@@H](CO)[C@@H](O)[C@H]1O`
ZINC3978047	0.739	267.2 Da LogP -1.98 TPSA 139.5	✓ Ro5	✓ Clean	`Nc1ncnc2c1ncn2[C@@H]1O[C@@H](CO)[C@H](O)[C@H]1O`
ZINC3978048	0.739	267.2 Da LogP -1.98 TPSA 139.5	✓ Ro5	✓ Clean	`Nc1ncnc2c1ncn2[C@H]1O[C@H](CO)[C@H](O)[C@H]1O`
ZINC3978049	0.739	267.2 Da LogP -1.98 TPSA 139.5	✓ Ro5	✓ Clean	`Nc1ncnc2c1ncn2[C@@H]1O[C@H](CO)[C@H](O)[C@H]1O`
ZINC4048240	0.739	267.2 Da LogP -1.98 TPSA 139.5	✓ Ro5	✓ Clean	`Nc1ncnc2c1ncn2[C@H]1O[C@H](CO)[C@@H](O)[C@H]1O`
ZINC4773848	0.739	266.3 Da LogP -2.01 TPSA 145.3	✓ Ro5	✓ Clean	`NC[C@@H]1O[C@H](n2cnc3c(N)ncnc32)[C@H](O)[C@@H]…`
ZINC4773849	0.739	266.3 Da LogP -2.01 TPSA 145.3	✓ Ro5	✓ Clean	`NC[C@@H]1O[C@@H](n2cnc3c(N)ncnc32)[C@H](O)[C@@H…`
ZINC4773850	0.739	266.3 Da LogP -2.01 TPSA 145.3	✓ Ro5	✓ Clean	`NC[C@@H]1O[C@H](n2cnc3c(N)ncnc32)[C@@H](O)[C@@H…`
ZINC4773851	0.739	266.3 Da LogP -2.01 TPSA 145.3	✓ Ro5	✓ Clean	`NC[C@@H]1O[C@@H](n2cnc3c(N)ncnc32)[C@@H](O)[C@@…`
ZINC77981211	0.739	266.3 Da LogP -2.01 TPSA 145.3	✓ Ro5	✓ Clean	`NC[C@H]1O[C@@H](n2cnc3c(N)ncnc32)[C@@H](O)[C@H]…`
ZINC82228511	0.739	266.3 Da LogP -2.01 TPSA 145.3	✓ Ro5	✓ Clean	`NC[C@H]1O[C@@H](n2cnc3c(N)ncnc32)[C@H](O)[C@H]1O`
ZINC8580514	0.739	267.2 Da LogP -1.98 TPSA 139.5	✓ Ro5	✓ Clean	`Nc1ncnc2c1ncn2[C@@H]1O[C@H](CO)[C@H](O)[C@@H]1O`
ZINC895113	0.739	267.2 Da LogP -1.98 TPSA 139.5	✓ Ro5	✓ Clean	`Nc1ncnc2c1ncn2[C@H]1O[C@@H](CO)[C@H](O)[C@@H]1O`
ZINC896706	0.739	267.2 Da LogP -1.98 TPSA 139.5	✓ Ro5	✓ Clean	`Nc1ncnc2c1ncn2[C@H]1O[C@@H](CO)[C@H](O)[C@H]1O`
ZINC970363	0.739	267.2 Da LogP -1.98 TPSA 139.5	✓ Ro5	✓ Clean	`Nc1ncnc2c1ncn2[C@@H]1O[C@H](CO)[C@@H](O)[C@@H]1O`
ZINC217503161	0.737	230.3 Da LogP 0.88 TPSA 92.4	✓ Ro5	✓ Clean	`CCCCC(=O)NCCCC[C@H](N)C(=O)O`
ZINC216616240	0.730	430.5 Da LogP 0.72 TPSA 184.8	1 viol.	✓ Clean	`N[C@@H](CCCCNC(=O)CCCCCCC(=O)NCCCC[C@H](N)C(=O)…`
ZINC28539127	0.725	328.5 Da LogP 3.61 TPSA 92.4	✓ Ro5	✓ Clean	`CCCCCCCCCCCC(=O)NCCCC[C@H](N)C(=O)O`
ZINC1081541	0.723	285.7 Da LogP -0.73 TPSA 119.3	✓ Ro5	✓ Clean	`Nc1ncnc2c1ncn2[C@@H]1O[C@H](CCl)[C@@H](O)[C@@H]…`
ZINC4188096	0.723	297.3 Da LogP -2.62 TPSA 159.8	✓ Ro5	✓ Clean	`Nc1ncnc2c1ncn2[C@H]1O[C@@H](CO)[C@@H](O)[C@@H](…`
ZINC4188103	0.723	297.3 Da LogP -2.62 TPSA 159.8	✓ Ro5	✓ Clean	`Nc1ncnc2c1ncn2[C@@H]1O[C@@H](CO)[C@@H](O)[C@@H]…`
ZINC4188112	0.723	297.3 Da LogP -2.62 TPSA 159.8	✓ Ro5	✓ Clean	`Nc1ncnc2c1ncn2[C@H]1O[C@@H](CO)[C@@H](O)[C@@H](…`
ZINC4188116	0.723	297.3 Da LogP -2.62 TPSA 159.8	✓ Ro5	✓ Clean	`Nc1ncnc2c1ncn2[C@@H]1O[C@@H](CO)[C@@H](O)[C@@H]…`
ZINC5941240	0.723	269.2 Da LogP -1.00 TPSA 119.3	✓ Ro5	✓ Clean	`Nc1ncnc2c1ncn2[C@@H]1O[C@H](CF)[C@@H](O)[C@H]1O`
ZINC5163039	0.712	340.4 Da LogP -0.89 TPSA 145.3	✓ Ro5	✓ Clean	`NCCCSC[C@H]1O[C@@H](n2cnc3c(N)ncnc32)[C@H](O)[C…`
ZINC73315774	0.704	381.5 Da LogP 1.73 TPSA 119.3	✓ Ro5	✓ Clean	`CCCCCCCSC[C@@H]1O[C@@H](n2cnc3c(N)ncnc32)[C@@H]…`

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.