Protein profile

PA2011

3-hydroxy-3-isohexenylglutaryl-CoA/hydroxy- methylglutaryl-CoA lyase

Genome: NC_002516.2

Gene: PA2011 liuE Structure source: Experimental + AlphaFold UniProt Q9I2A0
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Amino acids 300
Annotations 11
Features 13
PDB binders 5
Druggability 0.733

Overview

Basic information about this protein and its source genome.

Accession
PA2011
Assembly
Pseudomonas aeruginosa PAO1, complete genome
Gene
PA2011 liuE
Status
annotated
Amino acids
300
Structure source
Experimental + AlphaFold
EC
4.1.3.26 4.1.3.4
GO
GO:0047445 Catalysis of the reaction: 3-hydroxy-3-(4-methylpent-3-en-1-yl)glutaryl-CoA + 4 H+ = 7-methyl-3-oxooct-6-enoyl-CoA + acetate. GO:0004419 Catalysis of the reaction: (S)-3-hydroxy-3-methylglutaryl-CoA = acetoacetate + acetyl-CoA. GO:0046872 Binding to a metal ion. GO:0008300 The chemical reactions and pathways resulting in the breakdown of an isoprenoid compound, isoprene (2-methylbuta-1,3-diene) or compounds containing or derived from linked isoprene (3-methyl-2-butenylene) residues. GO:0046951 The chemical reactions and pathways resulting in the formation of ketone bodies, any one of the three substances: acetoacetate, D-3-hydroxybutyrate (beta-hydroxybutyrate) or acetone. Biosynthesis involves the formation of hydroxymethylglutaryl-CoA, which is cleaved to acetate and acetyl-CoA. GO:0006552 The chemical reactions and pathways resulting in the breakdown of L-leucine.

Target profile

Computed evidence for target prioritization.

Human off-target
hit
Human identity (%)
57.483
Human E-value
1.97e-128
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 0.733
Structure –
Pocket –

Sequence

Primary amino-acid sequence viewer.

MNLPKKVRLVEVGPRDGLQNEKQPIEVADKIRLVDDLSAAGLDYIEVGSFVSPKWVPQMAGSAEVFAGIRQRPGVTYAALAPNLKGFEAALESGVKEVAVFAAASEAFSQRNINCSIKDSLERFVPVLEAARQHQVRVRGYISCVLGCPYDGDVDPRQVAWVARELQQMGCYEVSLGDTIGVGTAGATRRLIEAVASEVPRERLAGHFHDTYGQALANIYASLLEGIAVFDSSVAGLGGCPYAKGATGNVASEDVLYLLNGLEIHTGVDMHALVDAGQRICAVLGKSNGSRAAKALLAKA

Functional Annotations

Enzyme classification and Gene Ontology terms linked to this protein.

2 EC 9 GO

Enzyme Commission (EC)

2

Gene Ontology (GO)

9
  • GO:0047445 Catalysis of the reaction: 3-hydroxy-3-(4-methylpent-3-en-1-yl)glutaryl-CoA + 4 H+ = 7-methyl-3-oxooct-6-enoyl-CoA + acetate.
  • GO:0004419 Catalysis of the reaction: (S)-3-hydroxy-3-methylglutaryl-CoA = acetoacetate + acetyl-CoA.
  • GO:0046872 Binding to a metal ion.
  • GO:0008300 The chemical reactions and pathways resulting in the breakdown of an isoprenoid compound, isoprene (2-methylbuta-1,3-diene) or compounds containing or derived from linked isoprene (3-methyl-2-butenylene) residues.
  • GO:0046951 The chemical reactions and pathways resulting in the formation of ketone bodies, any one of the three substances: acetoacetate, D-3-hydroxybutyrate (beta-hydroxybutyrate) or acetone. Biosynthesis involves the formation of hydroxymethylglutaryl-CoA, which is cleaved to acetate and acetyl-CoA.
  • GO:0006552 The chemical reactions and pathways resulting in the breakdown of L-leucine.
  • GO:0046247 The chemical reactions and pathways resulting in the breakdown of terpenes, any of a large group of hydrocarbons made up of isoprene units.
  • 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:0016833 Catalysis of the cleavage of a C-C bond by other means than by hydrolysis or oxidation, of a 3-hydroxy acid.

Sequence Features

Domain/signature hits from InterPro and related databases.

13 records
Show feature table
Start End DB Term Name
2 300 FunFam G3DSA:3.20.20.70:FF:000201 Hydroxymethylglutaryl-CoA lyase
2 298 PANTHER PTHR42738 HYDROXYMETHYLGLUTARYL-COA LYASE
2 298 InterPro IPR043594 HMG-CoA lyase
6 278 Pfam PF00682 HMGL-like
6 278 InterPro IPR000891 Pyruvate carboxyltransferase
1 300 Gene3D G3DSA:3.20.20.70 Aldolase class I
1 300 InterPro IPR013785 Aldolase-type TIM barrel
7 274 ProSiteProfiles PS50991 Pyruvate carboxyltransferase domain.
7 274 InterPro IPR000891 Pyruvate carboxyltransferase
1 289 SUPERFAMILY SSF51569 Aldolase
233 242 ProSitePatterns PS01062 Hydroxymethylglutaryl-coenzyme A lyase active site.
233 242 InterPro IPR000138 Hydroxymethylglutaryl-CoA lyase, active site
9 282 CDD cd07938 DRE_TIM_HMGL

3D Structure

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

3D visualization script Full viewer

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Structural evidence

1 + 1

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

Entry Method Resolution Chain Coverage Links Status
PDB 2FTP
X-ray 2.40 Å A
100.0% 1-300
PDBe RCSB PDBj File
Viewing
AlphaFold PA2011
AlphaFold — — 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 0.733
3 0.299

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 25.71 0.908
2 1.57 0.024
3 0.56 0.0

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.

44 records

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
3HG
2CW6
P35914 148.1 Da LogP -0.70 TPSA 94.8 ✓ Ro5 ✓ Clean C(C(CC(=O)O)O)C(=O)O
AKG
2ZTJ
O87198 146.1 Da LogP -0.50 TPSA 91.7 ✓ Ro5 ✓ Clean C(CC(=O)O)C(=O)C(=O)O
HCA
2ZTK
O87198 206.1 Da LogP -0.86 TPSA 132.1 ✓ Ro5 ✓ Clean C(C[C@@](CC(=O)O)(C(=O)O)O)C(=O)O
HGG
3MP3
P35914 897.6 Da LogP -2.11 TPSA 421.2 3 viol. ✓ Clean CC(C)(CO[P@](=O)(O)O[P@](=O)(O)OC[C@@H]1[C@H]([…
HMG
3MP5
P35914 906.6 Da LogP -5.58 TPSA 435.3 3 viol. ✓ Clean C[C@](CC(=O)[O-])(CC(=O)SCCNC(=O)CCNC(=O)[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.