Protein profile

PA3417

pyruvate dehydrogenase E1 component subunit alpha

Genome: NC_002516.2

Gene: PA3417 Structure source: AlphaFold UniProt Q9HYI8

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Amino acids 365

Annotations 4

Features 9

PDB binders 8

Druggability 0.72

Overview

Basic information about this protein and its source genome.

Accession: PA3417
Assembly: Pseudomonas aeruginosa PAO1, complete genome
Gene: PA3417
Status: annotated
Amino acids: 365
Structure source: AlphaFold

1.2.4.1

GO:0004739 Catalysis of the reaction: N(6)-[(R)-lipoyl]-L-lysyl-[protein] + pyruvate + H+ = N(6)-[(R)-S(8)-acetyldihydrolipoyl]-L-lysyl-[protein] + CO2. GO:0006086 The chemical reactions and pathways resulting in the formation of acetyl-CoA from pyruvate. In most organisms, this pathway links glycolysis to the TCA cycle, by a series of three reactions carried out by a multisubunit complex called the 'pyruvate dehydrogenase complex', even though pyruvate dehydrogenase activity describes only one of those reactions. The combination of the three reactions can be summarized as: pyruvate + coenzyme A + NAD+ -> acetyl-CoA + CO2 + NADH. GO:0016624 Catalysis of an oxidation-reduction (redox) reaction in which an aldehyde or ketone (oxo) group acts as a hydrogen or electron donor and reduces a disulfide.

Target profile

Computed evidence for target prioritization.

Human off-target: hit
Human identity (%): 32.67
Human E-value: 9.98e-50
Gut microbiome off-target: hit
Essential (DEG): N
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 0.72

Structure –

Pocket –

Sequence

Primary amino-acid sequence viewer.

MVHNRIDPPFTRYLDSDGRPLGELPAWAGDSDALVGLYRQMLLTRLFDQKAVALQRTGRIGTYAPTLGQEAIGVAIGSQMRAEDVLVPYYRDTAVQLMRGVRMEDILLYWGGDERGSDYAEPLAAQDFPICVPIATQALHACGVASAFRIRGEHRVAVTTCGDGATSKGDFLEALNVAGAWQLPVLFVVNNNQWAISVPRRIQCGAPTLAEKAVGAGFPGEQVDGNDVLAVAERVRAALERARQGKGPTLLECISYRLCDHTTADDASRYRSAEEVNQAWREEPIKRLRAFLAGRGQWDEEREQALVGECQARVQEAVERFETFAAQAPQALFEHVYARWPAVLEEQREQLLERAARRRGGAEHE

Functional Annotations

Enzyme classification and Gene Ontology terms linked to this protein.

1 EC 3 GO

Enzyme Commission (EC)

1.2.4.1

Gene Ontology (GO)

GO:0004739 Catalysis of the reaction: N(6)-[(R)-lipoyl]-L-lysyl-[protein] + pyruvate + H+ = N(6)-[(R)-S(8)-acetyldihydrolipoyl]-L-lysyl-[protein] + CO2.
GO:0006086 The chemical reactions and pathways resulting in the formation of acetyl-CoA from pyruvate. In most organisms, this pathway links glycolysis to the TCA cycle, by a series of three reactions carried out by a multisubunit complex called the 'pyruvate dehydrogenase complex', even though pyruvate dehydrogenase activity describes only one of those reactions. The combination of the three reactions can be summarized as: pyruvate + coenzyme A + NAD+ -> acetyl-CoA + CO2 + NADH.
GO:0016624 Catalysis of an oxidation-reduction (redox) reaction in which an aldehyde or ketone (oxo) group acts as a hydrogen or electron donor and reduces a disulfide.

Sequence Features

Domain/signature hits from InterPro and related databases.

9 records

Show feature table

Start	End	DB	Term	Name
2	351	Gene3D	G3DSA:3.40.50.970	-
10	350	NCBIfam	TIGR03181	pyruvate dehydrogenase (acetyl-transferring) E1 component subunit alpha
10	350	InterPro	IPR017596	Pyruvate dehydrogenase E1 component subunit alpha/BCKADH E1-alpha
30	352	SUPERFAMILY	SSF52518	Thiamin diphosphate-binding fold (THDP-binding)
30	352	InterPro	IPR029061	Thiamin diphosphate-binding fold
38	323	Pfam	PF00676	Dehydrogenase E1 component
38	323	InterPro	IPR001017	Dehydrogenase, E1 component
37	320	CDD	cd02000	TPP_E1_PDC_ADC_BCADC
9	356	PANTHER	PTHR43380	2-OXOISOVALERATE DEHYDROGENASE SUBUNIT ALPHA, MITOCHONDRIAL

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 PA3417	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
1				0.72
7				0.436

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.

59 records

Chemistry signal

Structural and bioactivity evidence are both available for this target.

Direct evidence 0 59 via homologs

Structural ligands 8 0 loaded crystals

Bioactive compounds 1 50 ZINC candidates

Drug-like & clean 53 4 PAINS alerts

Best available ligand signal

4MV PDB via homolog 116.2 Da · LogP 1.51 · TPSA 37.3

4MV PDB via homolog BEN PDB via homolog COI PDB via homolog PYR PDB via homolog

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
4MV	1UMC	Q5SLR4	116.2 Da LogP 1.51 TPSA 37.3	✓ Ro5	✓ Clean	`CC(C)CCC(=O)O`
BEN	1V11	P12694	120.2 Da LogP 0.97 TPSA 49.9	✓ Ro5	✓ Clean	`[H]/N=C(\c1ccccc1)/N`
COI	1QS0	P09060	130.1 Da LogP 0.69 TPSA 54.4	✓ Ro5	✓ Clean	`CC(C)CC(=O)C(=O)O`
PYR	3DV0	P21873	88.1 Da LogP -0.34 TPSA 54.4	✓ Ro5	✓ Clean	`CC(=O)C(=O)O`
THV	2BEU	P12694	496.4 Da LogP 1.75 TPSA 189.2	✓ Ro5	✓ Clean	`Cc1c(sc([n+]1Cc2cnc(nc2N)C)[C-](C(C)C)O)CCO[P@@…`
THW	2BEW	P12694	530.4 Da LogP 2.14 TPSA 189.2	1 viol.	✓ Clean	`Cc1c(sc([n+]1Cc2cnc(nc2N)C)[C-](c3ccccc3)O)CCO[…`
THY	2BEV	P12694	510.4 Da LogP 2.14 TPSA 189.2	1 viol.	✓ Clean	`CC[C@H](C)[C-](c1[n+](c(c(s1)CCO[P@](=O)(O)OP(=…`
TZD	2BFC	P12694	440.3 Da LogP 0.72 TPSA 187.1	✓ Ro5	✓ Clean	`Cc1ncc(c(n1)N)CN2C(=C(SC2=O)CCO[P@@](=O)(O)OP(=…`

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).

Ligand	UniProt (homolog)	pchembl	MW · LogP · TPSA	Lipinski	PAINS	SMILES
CHEMBL1061	P26284	—	223.3 Da LogP 1.29 TPSA 66.4	✓ Ro5	✓ Clean	`O=C1NC(=O)C(Cc2ccc(O)cc2)S1`

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
ZINC13540298	1.000	440.3 Da LogP 0.72 TPSA 187.1	✓ Ro5	✓ Clean	`Cc1ncc(Cn2c(C)c(CCO[P@@](=O)(O)OP(=O)(O)O)sc2=O…`
ZINC26575565	1.000	223.3 Da LogP 1.29 TPSA 66.4	✓ Ro5	✓ Clean	`O=C1NC(=O)[C@H](Cc2ccc(O)cc2)S1`
ZINC26575566	1.000	223.3 Da LogP 1.29 TPSA 66.4	✓ Ro5	✓ Clean	`O=C1NC(=O)[C@@H](Cc2ccc(O)cc2)S1`
ZINC1453005	0.750	241.7 Da LogP 2.23 TPSA 46.2	✓ Ro5	✓ Clean	`O=C1NC(=O)[C@H](Cc2ccc(Cl)cc2)S1`
ZINC1453006	0.750	241.7 Da LogP 2.23 TPSA 46.2	✓ Ro5	✓ Clean	`O=C1NC(=O)[C@@H](Cc2ccc(Cl)cc2)S1`
ZINC22059407	0.750	225.2 Da LogP 1.72 TPSA 46.2	✓ Ro5	✓ Clean	`O=C1NC(=O)[C@H](Cc2ccc(F)cc2)S1`
ZINC22059410	0.750	225.2 Da LogP 1.72 TPSA 46.2	✓ Ro5	✓ Clean	`O=C1NC(=O)[C@@H](Cc2ccc(F)cc2)S1`
ZINC136823231	0.727	286.1 Da LogP 2.34 TPSA 46.2	✓ Ro5	✓ Clean	`O=C1NC(=O)[C@@H](Cc2ccc(Br)cc2)S1`
ZINC136823276	0.727	286.1 Da LogP 2.34 TPSA 46.2	✓ Ro5	✓ Clean	`O=C1NC(=O)[C@H](Cc2ccc(Br)cc2)S1`
ZINC1395202	0.727	222.3 Da LogP 1.16 TPSA 72.2	✓ Ro5	Alert	`Nc1ccc(C[C@@H]2SC(=O)NC2=O)cc1`
ZINC1395203	0.727	222.3 Da LogP 1.16 TPSA 72.2	✓ Ro5	Alert	`Nc1ccc(C[C@H]2SC(=O)NC2=O)cc1`
ZINC1453011	0.727	221.3 Da LogP 1.89 TPSA 46.2	✓ Ro5	✓ Clean	`Cc1ccc(C[C@@H]2SC(=O)NC2=O)cc1`
ZINC1453012	0.727	221.3 Da LogP 1.89 TPSA 46.2	✓ Ro5	✓ Clean	`Cc1ccc(C[C@H]2SC(=O)NC2=O)cc1`
ZINC1453007	0.719	207.3 Da LogP 1.58 TPSA 46.2	✓ Ro5	✓ Clean	`O=C1NC(=O)[C@H](Cc2ccccc2)S1`
ZINC1453008	0.719	207.3 Da LogP 1.58 TPSA 46.2	✓ Ro5	✓ Clean	`O=C1NC(=O)[C@@H](Cc2ccccc2)S1`
ZINC33876997	0.686	239.3 Da LogP 0.99 TPSA 86.6	✓ Ro5	Alert	`O=C1NC(=O)[C@@H](Cc2ccc(O)c(O)c2)S1`
ZINC33876999	0.686	239.3 Da LogP 0.99 TPSA 86.6	✓ Ro5	Alert	`O=C1NC(=O)[C@H](Cc2ccc(O)c(O)c2)S1`
ZINC1386519	0.676	208.2 Da LogP 0.98 TPSA 59.1	✓ Ro5	✓ Clean	`O=C1NC(=O)[C@H](Cc2ccncc2)S1`
ZINC4052182	0.676	208.2 Da LogP 0.98 TPSA 59.1	✓ Ro5	✓ Clean	`O=C1NC(=O)[C@@H](Cc2ccncc2)S1`
ZINC144529043	0.667	223.3 Da LogP 1.29 TPSA 66.4	✓ Ro5	✓ Clean	`O=C1NC(=O)[C@H](Cc2cccc(O)c2)S1`
ZINC144529255	0.667	223.3 Da LogP 1.29 TPSA 66.4	✓ Ro5	✓ Clean	`O=C1NC(=O)[C@@H](Cc2cccc(O)c2)S1`
ZINC2152	0.667	280.4 Da LogP 0.48 TPSA 94.0	✓ Ro5	✓ Clean	`Cc1ncc(Cn2c(C)c(CCO)sc2=O)c(N)n1`
ZINC1841074	0.636	200.3 Da LogP 3.85 TPSA 37.3	✓ Ro5	✓ Clean	`CC(C)CCCCCCCCC(=O)O`
ZINC2013445	0.636	214.3 Da LogP 4.24 TPSA 37.3	✓ Ro5	✓ Clean	`CC(C)CCCCCCCCCC(=O)O`
ZINC2575042	0.636	228.4 Da LogP 4.63 TPSA 37.3	✓ Ro5	✓ Clean	`CC(C)CCCCCCCCCCC(=O)O`
ZINC218823900	0.632	257.7 Da LogP 1.94 TPSA 66.4	✓ Ro5	✓ Clean	`O=C1NC(=O)[C@H](Cc2ccc(O)c(Cl)c2)S1`
ZINC218823984	0.632	257.7 Da LogP 1.94 TPSA 66.4	✓ Ro5	✓ Clean	`O=C1NC(=O)[C@@H](Cc2ccc(O)c(Cl)c2)S1`
ZINC218824096	0.632	302.1 Da LogP 2.05 TPSA 66.4	✓ Ro5	✓ Clean	`O=C1NC(=O)[C@H](Cc2ccc(O)c(Br)c2)S1`
ZINC218824164	0.632	302.1 Da LogP 2.05 TPSA 66.4	✓ Ro5	✓ Clean	`O=C1NC(=O)[C@@H](Cc2ccc(O)c(Br)c2)S1`
ZINC8215517	0.627	425.3 Da LogP 0.84 TPSA 169.0	✓ Ro5	✓ Clean	`Cc1ncc(C[n+]2csc(CCO[P@@](=O)(O)OP(=O)(O)O)c2C)…`
ZINC1037079	0.615	265.3 Da LogP 1.51 TPSA 72.5	✓ Ro5	✓ Clean	`CC(=O)Oc1ccc(C[C@@H]2SC(=O)NC2=O)cc1`
ZINC1037080	0.615	265.3 Da LogP 1.51 TPSA 72.5	✓ Ro5	✓ Clean	`CC(=O)Oc1ccc(C[C@H]2SC(=O)NC2=O)cc1`
ZINC34472979	0.600	281.3 Da LogP 1.04 TPSA 92.7	✓ Ro5	✓ Clean	`O=C(O)COc1ccc(C[C@H]2SC(=O)NC2=O)cc1`
ZINC34472980	0.600	281.3 Da LogP 1.04 TPSA 92.7	✓ Ro5	✓ Clean	`O=C(O)COc1ccc(C[C@@H]2SC(=O)NC2=O)cc1`
ZINC148984399	0.585	253.3 Da LogP 1.29 TPSA 75.6	✓ Ro5	✓ Clean	`COc1cc(C[C@@H]2SC(=O)NC2=O)ccc1O`
ZINC148984633	0.585	253.3 Da LogP 1.29 TPSA 75.6	✓ Ro5	✓ Clean	`COc1cc(C[C@H]2SC(=O)NC2=O)ccc1O`
ZINC4108904	0.585	273.3 Da LogP 1.77 TPSA 64.0	✓ Ro5	✓ Clean	`O=C1NC(=O)[C@@H](Cc2ccc(-n3cccn3)cc2)S1`
ZINC4108906	0.585	273.3 Da LogP 1.77 TPSA 64.0	✓ Ro5	✓ Clean	`O=C1NC(=O)[C@H](Cc2ccc(-n3cccn3)cc2)S1`
ZINC145838685	0.583	200.3 Da LogP 3.70 TPSA 37.3	✓ Ro5	✓ Clean	`CC(C)CCC[C@@H](C)CCCC(=O)O`
ZINC145838882	0.583	200.3 Da LogP 3.70 TPSA 37.3	✓ Ro5	✓ Clean	`CC(C)CCC[C@H](C)CCCC(=O)O`
ZINC9109306	0.575	255.7 Da LogP 2.54 TPSA 46.2	✓ Ro5	✓ Clean	`Cc1ccc(C[C@H]2SC(=O)NC2=O)cc1Cl`
ZINC9109307	0.575	255.7 Da LogP 2.54 TPSA 46.2	✓ Ro5	✓ Clean	`Cc1ccc(C[C@@H]2SC(=O)NC2=O)cc1Cl`
ZINC1396290	0.564	222.3 Da LogP 1.16 TPSA 72.2	✓ Ro5	✓ Clean	`Nc1cccc(C[C@@H]2SC(=O)NC2=O)c1`
ZINC1396291	0.564	222.3 Da LogP 1.16 TPSA 72.2	✓ Ro5	✓ Clean	`Nc1cccc(C[C@H]2SC(=O)NC2=O)c1`
ZINC218823161	0.564	225.2 Da LogP 1.72 TPSA 46.2	✓ Ro5	✓ Clean	`O=C1NC(=O)[C@H](Cc2cccc(F)c2)S1`
ZINC218823233	0.564	225.2 Da LogP 1.72 TPSA 46.2	✓ Ro5	✓ Clean	`O=C1NC(=O)[C@@H](Cc2cccc(F)c2)S1`
ZINC218823522	0.564	241.7 Da LogP 2.23 TPSA 46.2	✓ Ro5	✓ Clean	`O=C1NC(=O)[C@H](Cc2cccc(Cl)c2)S1`
ZINC218823701	0.564	286.1 Da LogP 2.34 TPSA 46.2	✓ Ro5	✓ Clean	`O=C1NC(=O)[C@H](Cc2cccc(Br)c2)S1`
ZINC218823783	0.564	286.1 Da LogP 2.34 TPSA 46.2	✓ Ro5	✓ Clean	`O=C1NC(=O)[C@@H](Cc2cccc(Br)c2)S1`
ZINC33968825	0.564	335.5 Da LogP 3.88 TPSA 66.4	✓ Ro5	✓ Clean	`CC(C)(C)c1cc(C[C@H]2SC(=O)NC2=O)cc(C(C)(C)C)c1O`

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.