Protein profile

KP13_02614

2-isopropylmalate synthase

Genome: KpKP13

Gene: AHE43069.1 Structure source: AlphaFold + ColabFold UniProt A0A0H3H1U7
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Amino acids 558
Annotations 9
Features 27
PDB binders 8
Druggability 0.286

Overview

Basic information about this protein and its source genome.

Accession
KP13_02614
Assembly
Klebsiella pneumoniae subsp. pneumoniae Kp13, complete sequence
Gene
AHE43069.1
Status
annotated
Amino acids
558
Structure source
AlphaFold + ColabFold
EC
2.3.3.13
GO
GO:0019752 The chemical reactions and pathways involving carboxylic acids, any organic acid containing one or more carboxyl (COOH) groups or anions (COO-). GO:0003852 Catalysis of the reaction: 3-methyl-2-oxobutanoate + acetyl-CoA + H2O = (2S)-2-isopropylmalate + CoA + H+. GO:0009098 The chemical reactions and pathways resulting in the formation of L-leucine, 2-amino-4-methylpentanoic acid. 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. GO:0005737 The contents of a cell excluding the plasma membrane and nucleus, but including other subcellular structures.

Target profile

Computed evidence for target prioritization.

Human off-target
No hit
Human identity (%)
0.0
Gut microbiome off-target
hit
Essential (DEG)
Y
DEG identity (%)
49.634
DEG E-value
0.0
Localization
Cytoplasmic
ColabFold pLDDT
93.23

Selected Druggability evidence

AlphaFold / UniProt model

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 0.286
Structure A0A0H3H1U7
Pocket Pocket 7
P2Rank 0.708
Structure A0A0H3H1U7
Pocket Pocket 1
ColabFold model
FPocket 0.486 · Pocket 10
P2Rank 0.715 · Pocket 1
Core conservation Conserved core gene
Roary core
CoreCruncher core
Gut microbiome 129 / 4744 genomes with a hit
Normalized 0.027

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

Sequence Features

Domain/signature hits from InterPro and related databases.

27 records
Show feature table
Start End DB Term Name
1 552 PANTHER PTHR46911 -
420 549 Pfam PF08502 LeuA allosteric (dimerisation) domain
420 549 InterPro IPR013709 2-isopropylmalate synthase LeuA, allosteric (dimerisation) domain
10 374 Gene3D G3DSA:3.20.20.70 Aldolase class I
10 374 InterPro IPR013785 Aldolase-type TIM barrel
31 305 ProSiteProfiles PS50991 Pyruvate carboxyltransferase domain.
31 305 InterPro IPR000891 Pyruvate carboxyltransferase
375 551 Gene3D G3DSA:3.30.160.270 -
375 551 InterPro IPR036230 2-isopropylmalate synthase LeuA, allosteric (dimerisation) domain superfamily
5 551 NCBIfam TIGR00970 2-isopropylmalate synthase
5 551 InterPro IPR005668 2-isopropylmalate synthase
6 553 Hamap MF_00572 2-isopropylmalate synthase [leuA].
6 553 InterPro IPR005668 2-isopropylmalate synthase
31 311 Pfam PF00682 HMGL-like
31 311 InterPro IPR000891 Pyruvate carboxyltransferase
20 328 SUPERFAMILY SSF51569 Aldolase
30 312 CDD cd07942 DRE_TIM_LeuA
30 312 InterPro IPR039371 LeuA, N-terminal catalytic TIM barrel domain
38 54 ProSitePatterns PS00815 Alpha-isopropylmalate and homocitrate synthases signature 1.
38 54 InterPro IPR002034 Alpha-isopropylmalate/homocitrate synthase, conserved site
387 434 SUPERFAMILY SSF89000 post-HMGL domain-like
443 549 SUPERFAMILY SSF110921 2-isopropylmalate synthase LeuA, allosteric (dimerisation) domain
443 549 InterPro IPR036230 2-isopropylmalate synthase LeuA, allosteric (dimerisation) domain superfamily
420 552 SMART SM00917 LeuA_dimer_2
420 552 InterPro IPR013709 2-isopropylmalate synthase LeuA, allosteric (dimerisation) domain
241 254 ProSitePatterns PS00816 Alpha-isopropylmalate and homocitrate synthases signature 2.
241 254 InterPro IPR002034 Alpha-isopropylmalate/homocitrate synthase, conserved site

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

0 + 2

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

Entry Method Resolution Chain Coverage Links Status
AlphaFold AF_A0A0H3H1U7
AlphaFold — — full sequence — Viewing
ColabFold KP13_02614
ColabFold — — 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
7 0.286
2 0.251

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 12.84 0.664
2 5.39 0.255
3 1.14 0.009
4 1.01 0.006
5 0.81 0.003

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.