Protein profile

PA3792

2-isopropylmalate synthase

Genome: NC_002516.2

Gene: leuA PA3792 Structure source: AlphaFold UniProt Q9HXK5
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Amino acids 592
Annotations 9
Features 29
PDB binders 8
Druggability 0.288

Overview

Basic information about this protein and its source genome.

Accession
PA3792
Assembly
Pseudomonas aeruginosa PAO1, complete genome
Gene
leuA PA3792
Status
annotated
Amino acids
592
Structure source
AlphaFold
EC
2.3.3.13
GO
GO:0005737 The contents of a cell excluding the plasma membrane and nucleus, but including other subcellular structures. GO:0003852 Catalysis of the reaction: 3-methyl-2-oxobutanoate + acetyl-CoA + H2O = (2S)-2-isopropylmalate + CoA + H+. GO:0003985 Catalysis of the reaction: 2 acetyl-CoA = CoA + acetoacetyl-CoA. GO:0000287 Binding to a magnesium (Mg) ion. GO:0009098 The chemical reactions and pathways resulting in the formation of L-leucine, 2-amino-4-methylpentanoic acid. GO:0019752 The chemical reactions and pathways involving carboxylic acids, any organic acid containing one or more carboxyl (COOH) groups or anions (COO-).

Target profile

Computed evidence for target prioritization.

Human off-target
No hit
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 0.288
Structure –
Pocket –

Sequence

Primary amino-acid sequence viewer.

Functional Annotations

Enzyme classification and Gene Ontology terms linked to this protein.

1 EC 8 GO

Enzyme Commission (EC)

1

Gene Ontology (GO)

8
  • GO:0005737 The contents of a cell excluding the plasma membrane and nucleus, but including other subcellular structures.
  • GO:0003852 Catalysis of the reaction: 3-methyl-2-oxobutanoate + acetyl-CoA + H2O = (2S)-2-isopropylmalate + CoA + H+.
  • GO:0003985 Catalysis of the reaction: 2 acetyl-CoA = CoA + acetoacetyl-CoA.
  • GO:0000287 Binding to a magnesium (Mg) ion.
  • GO:0009098 The chemical reactions and pathways resulting in the formation of L-leucine, 2-amino-4-methylpentanoic acid.
  • GO:0019752 The chemical reactions and pathways involving carboxylic acids, any organic acid containing one or more carboxyl (COOH) groups or anions (COO-).
  • 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:0046912 Catalysis of the transfer of an acyl group from one compound (donor) to another (acceptor), with the acyl group being converted into alkyl on transfer.

Sequence Features

Domain/signature hits from InterPro and related databases.

29 records
Show feature table
Start End DB Term Name
69 349 Pfam PF00682 HMGL-like
69 349 InterPro IPR000891 Pyruvate carboxyltransferase
48 412 Gene3D G3DSA:3.20.20.70 Aldolase class I
48 412 InterPro IPR013785 Aldolase-type TIM barrel
44 585 Hamap MF_00572 2-isopropylmalate synthase [leuA].
44 585 InterPro IPR005668 2-isopropylmalate synthase
479 583 SUPERFAMILY SSF110921 2-isopropylmalate synthase LeuA, allosteric (dimerisation) domain
479 583 InterPro IPR036230 2-isopropylmalate synthase LeuA, allosteric (dimerisation) domain superfamily
76 92 ProSitePatterns PS00815 Alpha-isopropylmalate and homocitrate synthases signature 1.
76 92 InterPro IPR002034 Alpha-isopropylmalate/homocitrate synthase, conserved site
69 343 ProSiteProfiles PS50991 Pyruvate carboxyltransferase domain.
69 343 InterPro IPR000891 Pyruvate carboxyltransferase
458 584 SMART SM00917 LeuA_dimer_2
458 584 InterPro IPR013709 2-isopropylmalate synthase LeuA, allosteric (dimerisation) domain
38 590 PANTHER PTHR46911 -
69 351 CDD cd07942 DRE_TIM_LeuA
69 351 InterPro IPR039371 LeuA, N-terminal catalytic TIM barrel domain
458 583 Pfam PF08502 LeuA allosteric (dimerisation) domain
458 583 InterPro IPR013709 2-isopropylmalate synthase LeuA, allosteric (dimerisation) domain
413 583 Gene3D G3DSA:3.30.160.270 -
413 583 InterPro IPR036230 2-isopropylmalate synthase LeuA, allosteric (dimerisation) domain superfamily
47 412 FunFam G3DSA:3.20.20.70:FF:000045 2-isopropylmalate synthase
279 292 ProSitePatterns PS00816 Alpha-isopropylmalate and homocitrate synthases signature 2.
279 292 InterPro IPR002034 Alpha-isopropylmalate/homocitrate synthase, conserved site
424 473 SUPERFAMILY SSF89000 post-HMGL domain-like
413 583 FunFam G3DSA:3.30.160.270:FF:000006 2-isopropylmalate synthase
58 366 SUPERFAMILY SSF51569 Aldolase
43 584 NCBIfam TIGR00970 2-isopropylmalate synthase
43 584 InterPro IPR005668 2-isopropylmalate synthase

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
AlphaFold PA3792
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
3 0.288
10 0.231
17 0.221

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.

28 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
AKG
2ZTJ
O87198 146.1 Da LogP -0.50 TPSA 91.7 ✓ Ro5 ✓ Clean C(CC(=O)O)C(=O)C(=O)O
BPV
3HPZ
P9WQB3 167.0 Da LogP 0.03 TPSA 54.4 ✓ Ro5 ✓ Clean C(C(=O)C(=O)O)Br
COI
3HPS
P9WQB3 130.1 Da LogP 0.69 TPSA 54.4 ✓ Ro5 ✓ Clean CC(C)CC(=O)C(=O)O
FLC
3HQ1
P9WQB3 189.1 Da LogP -5.25 TPSA 140.6 ✓ Ro5 ✓ Clean C(C(=O)[O-])C(CC(=O)[O-])(C(=O)[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
KIV
4OV4
B0SN40 116.1 Da LogP 0.30 TPSA 54.4 ✓ Ro5 ✓ Clean CC(C)C(=O)C(=O)O
KMT
6E1J
C5J4P1 148.2 Da LogP 0.39 TPSA 54.4 ✓ Ro5 ✓ Clean CSCCC(=O)C(=O)O
VPM
4OV9
B0SN40 176.2 Da LogP -0.07 TPSA 94.8 ✓ Ro5 ✓ Clean CC(C)[C@@](CC(=O)O)(C(=O)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.