Protein profile

VK055_0988

fumarate hydratase, class II

Genome: KpATCC43816

Gene: AIK79612.1 fumC Structure source: AlphaFold + ColabFold UniProt A0A0H3GWS1
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Amino acids 456
Annotations 10
Features 30
PDB binders 9
Druggability 0.806

Overview

Basic information about this protein and its source genome.

Accession
VK055_0988
Assembly
Klebsiella pneumoniae subsp. pneumoniae strain ATCC 43816 KPPR1, complete genome
Gene
AIK79612.1 fumC
Status
annotated
Amino acids
456
Structure source
AlphaFold + ColabFold
EC
4.2.1.2
GO
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:0006106 The chemical reactions and pathways involving fumarate, the anion of trans-1,2-ethenedicarboxylic acid, the diastereoisomer of maleate. It is a key intermediate in metabolism and is formed in the TCA cycle from succinate and converted into malate. GO:0045239 Any of the heteromeric enzymes that act in the TCA cycle. GO:0016829 Catalysis of the cleavage of C-C, C-O, C-N and other bonds by other means than by hydrolysis or oxidation, or conversely adding a group to a double bond. They differ from other enzymes in that two substrates are involved in one reaction direction, but only one in the other direction. When acting on the single substrate, a molecule is eliminated and this generates either a new double bond or a new ring. GO:0004333 Catalysis of the reaction: (S)-malate = fumarate + H2O. GO:0006099 A nearly universal metabolic pathway in which the acetyl group of acetyl coenzyme A is effectively oxidized to two CO2 and four pairs of electrons are transferred to coenzymes. The acetyl group combines with oxaloacetate to form citrate, which undergoes successive transformations to isocitrate, 2-oxoglutarate, succinyl-CoA, succinate, fumarate, malate, and oxaloacetate again, thus completing the cycle. In eukaryotes the tricarboxylic acid is confined to the mitochondria. See also glyoxylate cycle.

Target profile

Computed evidence for target prioritization.

Human off-target
hit
Human identity (%)
61.858
Human E-value
2.48e-175
Gut microbiome off-target
hit
Essential (DEG)
Y
DEG identity (%)
61.674
DEG E-value
0.0
Localization
Cytoplasmic
ColabFold pLDDT
97.34

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 0.806
Structure A0A0H3GWS1
Pocket Pocket 5
P2Rank 0.124
Structure A0A0H3GWS1
Pocket Pocket 1
ColabFold model
FPocket 0.668 · Pocket 14
P2Rank 0.336 · Pocket 1
Core conservation Conserved core gene
Roary core
CoreCruncher core
Gut microbiome 939 / 4744 genomes with a hit
Normalized 0.198

Sequence

Primary amino-acid sequence viewer.

Functional Annotations

Enzyme classification and Gene Ontology terms linked to this protein.

1 EC 9 GO

Enzyme Commission (EC)

1

Gene Ontology (GO)

9
  • 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:0006106 The chemical reactions and pathways involving fumarate, the anion of trans-1,2-ethenedicarboxylic acid, the diastereoisomer of maleate. It is a key intermediate in metabolism and is formed in the TCA cycle from succinate and converted into malate.
  • GO:0045239 Any of the heteromeric enzymes that act in the TCA cycle.
  • GO:0016829 Catalysis of the cleavage of C-C, C-O, C-N and other bonds by other means than by hydrolysis or oxidation, or conversely adding a group to a double bond. They differ from other enzymes in that two substrates are involved in one reaction direction, but only one in the other direction. When acting on the single substrate, a molecule is eliminated and this generates either a new double bond or a new ring.
  • GO:0004333 Catalysis of the reaction: (S)-malate = fumarate + H2O.
  • GO:0006099 A nearly universal metabolic pathway in which the acetyl group of acetyl coenzyme A is effectively oxidized to two CO2 and four pairs of electrons are transferred to coenzymes. The acetyl group combines with oxaloacetate to form citrate, which undergoes successive transformations to isocitrate, 2-oxoglutarate, succinyl-CoA, succinate, fumarate, malate, and oxaloacetate again, thus completing the cycle. In eukaryotes the tricarboxylic acid is confined to the mitochondria. See also glyoxylate cycle.
  • GO:0005737 The contents of a cell excluding the plasma membrane and nucleus, but including other subcellular structures.
  • GO:0042802 Binding to an identical protein or proteins.
  • GO:0006108 The chemical reactions and pathways involving malate, the anion of hydroxybutanedioic acid, a chiral hydroxydicarboxylic acid. The (+) enantiomer is an important intermediate in metabolism as a component of both the TCA cycle and the glyoxylate cycle.

Sequence Features

Domain/signature hits from InterPro and related databases.

30 records
Show feature table
Start End DB Term Name
398 450 Pfam PF10415 Fumarase C C-terminus
398 450 InterPro IPR018951 Fumarase C, C-terminal
398 454 Gene3D G3DSA:1.10.40.30 -
1 451 PANTHER PTHR11444 ASPARTATEAMMONIA/ARGININOSUCCINATE/ADENYLOSUCCINATE LYASE
1 451 InterPro IPR005677 Fumarate hydratase, class II
170 188 PRINTS PR00149 Fumarate lyase superfamily signature
170 188 InterPro IPR000362 Fumarate lyase family
307 323 PRINTS PR00149 Fumarate lyase superfamily signature
307 323 InterPro IPR000362 Fumarate lyase family
261 288 PRINTS PR00149 Fumarate lyase superfamily signature
261 288 InterPro IPR000362 Fumarate lyase family
124 142 PRINTS PR00149 Fumarate lyase superfamily signature
124 142 InterPro IPR000362 Fumarate lyase family
397 454 FunFam G3DSA:1.10.40.30:FF:000002 Fumarate hydratase class II
129 396 FunFam G3DSA:1.20.200.10:FF:000001 Fumarate hydratase, mitochondrial
1 451 NCBIfam TIGR00979 class II fumarate hydratase
1 449 SUPERFAMILY SSF48557 L-aspartase-like
1 449 InterPro IPR008948 L-Aspartase-like
129 397 Gene3D G3DSA:1.20.200.10 Fumarase/aspartase (Central domain)
1 452 Hamap MF_00743 Fumarate hydratase class II [fumC].
1 452 InterPro IPR005677 Fumarate hydratase, class II
1 128 Gene3D G3DSA:1.10.275.10 -
1 128 InterPro IPR024083 Fumarase/histidase, N-terminal
2 332 Pfam PF00206 Lyase
2 332 InterPro IPR022761 Fumarate lyase, N-terminal
1 449 CDD cd01362 Fumarase_classII
1 449 InterPro IPR005677 Fumarate hydratase, class II
1 128 FunFam G3DSA:1.10.275.10:FF:000001 Fumarate hydratase, mitochondrial
307 316 ProSitePatterns PS00163 Fumarate lyases signature.
307 316 InterPro IPR020557 Fumarate lyase, 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_A0A0H3GWS1
AlphaFold — — full sequence — Viewing
ColabFold VK055_0988
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
5 0.806

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 2.59 0.074
2 1.23 0.012
3 0.9 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.

59 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
APO
7LUB
P07954 169.1 Da LogP -1.42 TPSA 120.8 ✓ Ro5 ✓ Clean C([C@H](C(=O)O)N)P(=O)(O)O
FLC
6P3C
P05042 189.1 Da LogP -5.25 TPSA 140.6 ✓ Ro5 ✓ Clean C(C(=O)[O-])C(CC(=O)[O-])(C(=O)[O-])O
FUM
7C18
Q65UJ3 116.1 Da LogP -0.29 TPSA 74.6 ✓ Ro5 ✓ Clean C(=C/C(=O)O)\C(=O)O
LMR
6U4O
A0A3Q0KQY7 134.1 Da LogP -1.09 TPSA 94.8 ✓ Ro5 ✓ Clean C([C@@H](C(=O)O)O)C(=O)O
MLI
3GTD
Q9ZCQ4 102.0 Da LogP -3.12 TPSA 80.3 ✓ Ro5 ✓ Clean C(C(=O)[O-])C(=O)[O-]
MLT
1FUO
P05042 134.1 Da LogP -1.09 TPSA 94.8 ✓ Ro5 ✓ Clean C([C@H](C(=O)O)O)C(=O)O
PMA
1FUP
P05042 254.1 Da LogP 0.48 TPSA 149.2 ✓ Ro5 ✓ Clean c1c(c(cc(c1C(=O)O)C(=O)O)C(=O)O)C(=O)O
SIF
1FUQ
P05042 190.3 Da LogP 1.25 TPSA 74.6 ✓ Ro5 ✓ Clean C[Si](C)(C)C(CC(=O)O)C(=O)O
TLA
6VBE
P07954 150.1 Da LogP -2.12 TPSA 115.1 ✓ Ro5 ✓ Clean [C@@H]([C@H](C(=O)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.