Target Pathogen

Overview

Basic information about this protein and its source genome.

Accession: PA2248
Assembly: Pseudomonas aeruginosa PAO1, complete genome
Gene: bkdA2 PA2248
Status: annotated
Amino acids: 350
Structure source: AlphaFold

EC

1.2.4.4

GO

GO:0003863 Catalysis of the reaction: N(6)-[(R)-lipoyl]-L-lysyl-[dihydrolipoyllysine-residue (2-methylpropanoyl)transferase] + 3-methyl-2-oxobutanoate + H+ = N(6)-[(R)-S(8)-2-methylpropanoyldihydrolipoyl]-L-lysyl-[dihydrolipoyllysine-residue (2-methylpropanoyl)transferase] + CO2. Also acts on 4-methyl-2-oxopentanoate and (S)-3-methyl-2-oxopentanoate, so that it acts on the 2-oxo acids that derive from the action of transaminases on valine, leucine and isoleucine. GO:0009083 The chemical reactions and pathways resulting in the breakdown of amino acids containing a branched carbon skeleton, comprising isoleucine, leucine and valine. GO:0007584 Any process that results in a change in state or activity of a cell or an organism (in terms of movement, secretion, enzyme production, gene expression, etc.) as a result of a nutrient stimulus. 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.

Target profile

Computed evidence for target prioritization.

Human off-target: hit
Human identity (%): 42.857
Human E-value: 2.38e-96
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 0.479

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

1.2.4.4

Gene Ontology (GO)

4

GO:0003863 Catalysis of the reaction: N(6)-[(R)-lipoyl]-L-lysyl-[dihydrolipoyllysine-residue (2-methylpropanoyl)transferase] + 3-methyl-2-oxobutanoate + H+ = N(6)-[(R)-S(8)-2-methylpropanoyldihydrolipoyl]-L-lysyl-[dihydrolipoyllysine-residue (2-methylpropanoyl)transferase] + CO2. Also acts on 4-methyl-2-oxopentanoate and (S)-3-methyl-2-oxopentanoate, so that it acts on the 2-oxo acids that derive from the action of transaminases on valine, leucine and isoleucine.
GO:0009083 The chemical reactions and pathways resulting in the breakdown of amino acids containing a branched carbon skeleton, comprising isoleucine, leucine and valine.
GO:0007584 Any process that results in a change in state or activity of a cell or an organism (in terms of movement, secretion, enzyme production, gene expression, etc.) as a result of a nutrient stimulus.
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.

Sequence Features

Domain/signature hits from InterPro and related databases.

17 records

Show feature table

Start	End	DB	Term	Name
222	349	FunFam	G3DSA:3.40.50.920:FF:000001	Pyruvate dehydrogenase E1 beta subunit
14	221	FunFam	G3DSA:3.40.50.970:FF:000001	Pyruvate dehydrogenase E1 beta subunit
13	216	Gene3D	G3DSA:3.40.50.970	-
5	349	PANTHER	PTHR42980	2-OXOISOVALERATE DEHYDROGENASE SUBUNIT BETA-RELATED
17	192	SMART	SM00861	Transket_pyr_3
17	192	InterPro	IPR005475	Transketolase-like, pyrimidine-binding domain
224	340	Pfam	PF02780	Transketolase, C-terminal domain
224	340	InterPro	IPR033248	Transketolase, C-terminal domain
16	191	Pfam	PF02779	Transketolase, pyrimidine binding domain
16	191	InterPro	IPR005475	Transketolase-like, pyrimidine-binding domain
218	348	SUPERFAMILY	SSF52922	TK C-terminal domain-like
218	348	InterPro	IPR009014	Transketolase C-terminal/Pyruvate-ferredoxin oxidoreductase domain II
21	187	CDD	cd07036	TPP_PYR_E1-PDHc-beta_like
217	350	Gene3D	G3DSA:3.40.50.920	-
217	350	InterPro	IPR009014	Transketolase C-terminal/Pyruvate-ferredoxin oxidoreductase domain II
16	231	SUPERFAMILY	SSF52518	Thiamin diphosphate-binding fold (THDP-binding)
16	231	InterPro	IPR029061	Thiamin diphosphate-binding fold

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 PA2248	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				0.479

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.

21 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
4MV	1UMC	Q5SLR3	116.2 Da LogP 1.51 TPSA 37.3	✓ Ro5	✓ Clean	`CC(C)CCC(=O)O`
A5X	6CFO	P11177	533.4 Da LogP 0.47 TPSA 226.5	2 viol.	✓ Clean	`Cc1c(sc([n+]1Cc2cnc(nc2N)C)[C@@](C)(O)P(=O)O)CC…`
COI	1QS0	P09061	130.1 Da LogP 0.69 TPSA 54.4	✓ Ro5	✓ Clean	`CC(C)CC(=O)C(=O)O`
PYR	3DV0	P21874	88.1 Da LogP -0.34 TPSA 54.4	✓ Ro5	✓ Clean	`CC(=O)C(=O)O`
THV	2BEU	P21953	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	P21953	530.4 Da LogP 2.14 TPSA 189.2	1 viol.	✓ Clean	`Cc1c(sc([n+]1Cc2cnc(nc2N)C)[C-](c3ccccc3)O)CCO[…`
THY	2BEV	P21953	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	P21953	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).

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
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`
ZINC8215517	0.618	425.3 Da LogP 0.84 TPSA 169.0	✓ Ro5	✓ Clean	`Cc1ncc(C[n+]2csc(CCO[P@@](=O)(O)OP(=O)(O)O)c2C)…`
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`
ZINC13540298	0.556	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…`
ZINC2492519	0.542	201.3 Da LogP 2.08 TPSA 40.5	✓ Ro5	✓ Clean	`CC(C)CN(CCC(=O)O)CC(C)C`
ZINC1532839	0.529	345.3 Da LogP 0.72 TPSA 122.4	✓ Ro5	✓ Clean	`Cc1ncc(C[n+]2csc(CCOP(=O)(O)O)c2C)c(N)n1`
ZINC13520374	0.528	426.3 Da LogP 0.97 TPSA 163.2	✓ Ro5	✓ Clean	`Cc1ncc(C[n+]2csc(CCO[P@@](=O)(O)OP(=O)(O)O)c2C)…`
ZINC1690029	0.524	204.2 Da LogP 0.42 TPSA 111.9	✓ Ro5	✓ Clean	`O=C(O)CCC(CCC(=O)O)C(=O)O`
ZINC96509633	0.522	228.2 Da LogP 1.89 TPSA 74.6	✓ Ro5	✓ Clean	`O=C(O)CCC(CCC(=O)O)C(F)(F)F`
ZINC4784097	0.500	201.3 Da LogP 1.40 TPSA 66.4	✓ Ro5	✓ Clean	`CC(C)CCNC(=O)CCCC(=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.

PA2248