Protein target profile

PA3454

acyl-CoA thiolase

Genome: NC_002516.2

Gene: PA3454 3D evidence: Experimental + AlphaFold DB model UniProt Q9HYF2
Export view
Length 394
Pocket druggability 0.709
Ligand records 61
EC / GO 1 / 7
Target summary

Target candidate with partial support; inspect missing evidence before prioritizing.

4 signals

Strengths

Strong predicted binding pocket FPocket selected-pocket score 0.71. This is a computational pocket signal, not binding validation. Structure available Experimental + AlphaFold DB model Ligand evidence via structure/bioactivity 11 structural and 0 bioactivity records.

Risks / watch

Human similarity Top human hit identity: 45.78%.

Missing evidence

No metabolic context No SBML/network-derived reaction evidence is loaded for this protein.
How to read this page

PDB: experimentally determined structures from the Protein Data Bank. These are the strongest structural evidence, but may cover only part of the protein.

AlphaFold DB model: a precomputed predicted structure downloaded from AlphaFold Database/UniProt, not an experiment performed here.

ColabFold model: a predicted structure generated for this workspace; interpret it with coverage and confidence.

pLDDT: confidence score for predicted structures. High values support local geometry; low values mean the region should not drive pocket interpretation.

FPocket / P2Rank: software tools that predict possible ligand-binding pockets on a 3D structure. They are useful screening signals, not experimental validation.

Druggability: a pocket-based estimate of whether a small molecule could bind productively. It does not mean a drug already exists.

PDB ligand: a compound observed in an experimental structure. Direct same-protein records are stronger than homolog-transferred records.

ChEMBL: a public database of measured compound bioactivity. Direct entries are stronger than entries transferred from similar proteins.

ZINC: a purchasable-compound database. Here it marks proposed candidates from chemical similarity, not measured binders.

LigQ / LigQ_2: an internal TPW pipeline step that gathers PDB, ChEMBL, and ZINC ligand evidence for each protein.

Off-target: sequence similarity to proteins we prefer not to hit, such as human proteins or beneficial gut microbiome proteins.

DEG: Database of Essential Genes. A match suggests the protein resembles genes known to be essential in other organisms.

Roary / CoreCruncher: pan-genome tools used to decide whether a gene is core across analyzed strains or accessory/strain-specific.

EC / GO: functional annotations: EC describes enzyme reactions; GO describes biological process, molecular function, or cellular component.

KEGG pathway: a curated metabolic route label used here to group reactions imported from the metabolic model.

Chokepoint: a metabolic reaction that is the only producer or consumer of a metabolite in the imported model.

Overview

Basic information about this protein and its source genome.

Accession
PA3454
Assembly
Pseudomonas aeruginosa PAO1, complete genome
Gene
PA3454
Status
annotated
Amino acids
394
3D evidence
Experimental + AlphaFold DB model
EC
2.3.1.16
GO
GO:0005737 The contents of a cell excluding the plasma membrane and nucleus, but including other subcellular structures. GO:0033812 Catalysis of the reaction: succinyl-CoA + acetyl-CoA = CoA + 3-oxoadipyl-CoA. GO:0003988 Catalysis of the reaction: acyl-CoA + acetyl-CoA = CoA + 3-oxoacyl-CoA. GO:0006635 A fatty acid oxidation process that results in the complete oxidation of a long-chain fatty acid. Fatty acid beta-oxidation begins with the addition of coenzyme A to a fatty acid, and occurs by successive cycles of reactions during each of which the fatty acid is shortened by a two-carbon fragment removed as acetyl coenzyme A; the cycle continues until only two or three carbons remain (as acetyl-CoA or propionyl-CoA respectively). GO:0010124 The chemical reactions and pathways resulting in the breakdown of phenylacetate. GO:0016746 Catalysis of the transfer of an acyl group from one compound (donor) to another (acceptor).

Target profile

Computed evidence for target prioritization.

Human off-target
hit
Human identity (%)
45.78
Human E-value
5.020000000000001e-103
Gut microbiome off-target
hit
Essential (DEG)
Y
Localization
Cytoplasmic

Selected pocket evidence

The selected pocket score is the FPocket value used for ranking after applying the curated structure priority. It estimates small-molecule pocket quality; it is not experimental binding evidence. The 3D viewer may show a different loaded structure, so visible pockets can differ.

FPocket 0.709
Structure –
Pocket –

Sequence

Primary amino-acid sequence viewer.

MREVVIVDSVRTGLAKSFRGKFNLTRPDDMAAHCVDALLARNDLDPLLVDDCIVGAGSNEGAQGHNIGRNVAVLSGLGIQVPGMTLNRYCSSGLQAIAIAANQIASGCSEVIVAGGVESITLTLKSVNTDHLVNPLLQREVPGIYYPMGQTAEIVARRYGITREAQDAYALQSQQRMARAQADGLFADEIVPMTTRYAVEDKASGEKQVLDGVVDRDDCNRPDTTLEGLASLKPAFAEDGSVTAGNASQLSDGASMTLLMSLEKALALGLEPKAFFRGFTVAGCEPDEMGIGPVFSVPKLLKAKGLKIADVDLWELNEAFASQCLYCRDRLEIDNEKYNVNGGSIAIGHPFGMTGSRQVGHLVRELHRRNLRYGVVTMCVGGGMGASGLFEAVR

Functional Annotations

Enzyme classification and Gene Ontology terms linked to this protein.

1 EC 7 GO

Enzyme Commission (EC)

1

Gene Ontology (GO)

7
  • GO:0005737 The contents of a cell excluding the plasma membrane and nucleus, but including other subcellular structures.
  • GO:0033812 Catalysis of the reaction: succinyl-CoA + acetyl-CoA = CoA + 3-oxoadipyl-CoA.
  • GO:0003988 Catalysis of the reaction: acyl-CoA + acetyl-CoA = CoA + 3-oxoacyl-CoA.
  • GO:0006635 A fatty acid oxidation process that results in the complete oxidation of a long-chain fatty acid. Fatty acid beta-oxidation begins with the addition of coenzyme A to a fatty acid, and occurs by successive cycles of reactions during each of which the fatty acid is shortened by a two-carbon fragment removed as acetyl coenzyme A; the cycle continues until only two or three carbons remain (as acetyl-CoA or propionyl-CoA respectively).
  • GO:0010124 The chemical reactions and pathways resulting in the breakdown of phenylacetate.
  • GO:0016746 Catalysis of the transfer of an acyl group from one compound (donor) to another (acceptor).
  • GO:0016747 Catalysis of the transfer of an acyl group, other than amino-acyl, from one compound (donor) to another (acceptor).

Sequence Features

Domain/signature hits from InterPro and related databases.

26 records
Show feature table
Start End DB Term Name
5 392 CDD cd00751 thiolase
5 392 InterPro IPR002155 Thiolase
271 391 SUPERFAMILY SSF53901 Thiolase-like
271 391 InterPro IPR016039 Thiolase-like
86 104 ProSitePatterns PS00098 Thiolases acyl-enzyme intermediate signature.
86 104 InterPro IPR020615 Thiolase, acyl-enzyme intermediate active site
4 276 Gene3D G3DSA:3.40.47.10 -
4 276 InterPro IPR016039 Thiolase-like
1 393 FunFam G3DSA:3.40.47.10:FF:000010 Acetyl-CoA acetyltransferase (Thiolase)
2 393 PANTHER PTHR43853 3-KETOACYL-COA THIOLASE, PEROXISOMAL
1 394 PIRSF PIRSF000429 Ac-CoA_Ac_transf
1 394 InterPro IPR002155 Thiolase
126 386 Gene3D G3DSA:3.40.47.10 -
126 386 InterPro IPR016039 Thiolase-like
271 391 Pfam PF02803 Thiolase, C-terminal domain
271 391 InterPro IPR020617 Thiolase, C-terminal
374 387 ProSitePatterns PS00099 Thiolases active site.
374 387 InterPro IPR020610 Thiolase, active site
1 265 SUPERFAMILY SSF53901 Thiolase-like
1 265 InterPro IPR016039 Thiolase-like
339 355 ProSitePatterns PS00737 Thiolases signature 2.
339 355 InterPro IPR020613 Thiolase, conserved site
6 391 NCBIfam TIGR01930 acetyl-CoA C-acyltransferase
6 391 InterPro IPR002155 Thiolase
4 261 Pfam PF00108 Thiolase, N-terminal domain
4 261 InterPro IPR020616 Thiolase, N-terminal

3D Structure

Selected loaded structure. Experimental PDB entries may cover only a portion of the sequence; AlphaFold DB and ColabFold models typically cover the full protein but remain computational predictions.

3D visualization script Full viewer

Loading 3D structure...

Legend High Medium Low

Structural evidence

1 + 1

Experimental PDB entries plus predicted AlphaFold DB or ColabFold models. Click Switch to display a different loaded structure in the viewer.

Entry Method Resolution Chain Coverage Links Status
PDB 8GQG
X-ray 1.80 Å A,B,C,D,E,F
100.0% 1-394
PDBe RCSB PDBj File
Viewing
AlphaFold DB PA3454
AlphaFold DB — — 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
1 0.513
2 0.512
3 0.267

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 8.23 0.438
2 2.61 0.075
3 2.55 0.072
4 1.85 0.036
5 0.88 0.004

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
Chemistry signal

Structural ligand evidence is available for this target.

Direct evidence 0 61 via homologs
Structural ligands 11 0 loaded crystals
Bioactive compounds 0 50 ZINC proposed compounds
Drug-like & clean 14 0 PAINS alerts
Best available ligand signal
168 PDB via homolog 388.5 Da · LogP 0.15 · TPSA 131.0 Open detail RCSB PDB
Detail RCSB PDB 168 PDB via homolog
Detail RCSB PDB 1VU PDB via homolog
Detail RCSB PDB 5UG PDB via homolog
Detail RCSB PDB CAA PDB via homolog

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.

Show only:
Ligand Source crystal UniProt (homolog) MW · LogP · TPSA Lipinski PAINS SMILES
168 RCSB PDB
1OU6
P07097 388.5 Da LogP 0.15 TPSA 131.0 ✓ Ro5 ✓ Clean CC(=O)OCCNC(=O)CCNC(=O)[C@@H](C(C)(C)COC(=O)C(C…
1VU RCSB PDB
6BJB
F1KYX0 823.6 Da LogP -0.93 TPSA 363.6 3 viol. ✓ Clean CCC(=O)SCCNC(=O)CCNC(=O)[C@@H](C(C)(C)COP(=O)(O…
5UG RCSB PDB
5F38
P76461 438.3 Da LogP -0.85 TPSA 191.7 1 viol. ✓ Clean CC(C)(COP(=O)(O)OP(=O)(O)O)[C@@H](C(=O)NCCC(=O)…
CAA RCSB PDB
1M1O
P07097 851.6 Da LogP -1.36 TPSA 380.7 3 viol. ✓ Clean CC(=O)CC(=O)SCCNC(=O)CCNC(=O)[C@@H](C(C)(C)CO[P…
COZ RCSB PDB
5F38
P76461 767.5 Da LogP -1.67 TPSA 346.6 3 viol. ✓ Clean CC(C)(CO[P@](=O)(O)O[P@](=O)(O)OC[C@@H]1[C@H]([…
DNO RCSB PDB
2WKU
P07097 180.2 Da LogP -3.38 TPSA 118.2 ✓ Ro5 ✓ Clean C([C@H]([C@H]([C@@H]([C@@H](C=O)O)O)O)O)O
DTT RCSB PDB
4C2K
P42765 154.3 Da LogP -0.43 TPSA 40.5 ✓ Ro5 ✓ Clean C([C@@H]([C@H](CS)O)O)S
O8Y RCSB PDB
6PCC
Q88N39 100.2 Da LogP 1.77 TPSA 17.1 ✓ Ro5 ✓ Clean CCCCCC=O
OPI RCSB PDB
2VU1
P07097 346.4 Da LogP -0.42 TPSA 125.0 ✓ Ro5 ✓ Clean CC(C)(C)C(=O)OCC(C)(C)[C@H](C(=O)NCCC(=O)NCCO)O
OYA RCSB PDB
6PCD
Q88N39 128.2 Da LogP 2.55 TPSA 17.1 ✓ Ro5 ✓ Clean CCCCCCCC=O
PN5 RCSB PDB
2VU2
P07097 362.5 Da LogP 0.52 TPSA 104.7 ✓ Ro5 ✓ Clean CC(C)(C)C(=O)OCC(C)(C)[C@H](C(=O)NCCC(=O)NCCS)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.