L-glutamic acid   Click here for help

GtoPdb Ligand ID: 1369

Synonyms: L-Glu | L-glutamate | poly-L-glutamate
PDB Ligand
Compound class: Metabolite
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Ligand Activity Visualisation Charts

These are box plot that provide a unique visualisation, summarising all the activity data for a ligand taken from ChEMBL and GtoPdb across multiple targets and species. Click on a plot to see the median, interquartile range, low and high data points. A value of zero indicates that no data are available. A separate chart is created for each target, and where possible the algorithm tries to merge ChEMBL and GtoPdb targets by matching them on name and UniProt accession, for each available species. However, please note that inconsistency in naming of targets may lead to data for the same target being reported across multiple charts.

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View interactive charts of activity data across species

IUPHAR Pharmacology Education Project (PEP) logo

View more information in the IUPHAR Pharmacology Education Project: glutamate

2D Structure
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2D Structure

An image of the ligand's 2D structure. For small molecules with SMILES these are drawn using the NCI/CADD Chemical Identifier Resolver. Click on the image to access the chemical structure search tool with the ligand pre-loaded in the structure editor. For other types of ligands, e.g. longer nucleotides and peptides, a manually drawn representation of the molecule may be provided.

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Physico-chemical Properties
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Physico-chemical Properties

Calculated molecular properties are available for small molecules and natural products (not peptides). Properties were generated using the Chemistry Development Kit (CDK) (Willighagen EL et al. Journal of Cheminformatics vol. 9:33. 2017, doi:10.1186/s13321-017-0220-4; https://cdk.github.io/). All properties were selected to enable the prediction of the Lipinski Rule-of-Five profile or ‘druglikeness’ for each ligand. For more info on each category see the help pages.

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Hydrogen bond acceptors 5
Hydrogen bond donors 3
Rotatable bonds 4
Topological polar surface area 100.62
Molecular weight 147.05
XLogP -3.35
No. Lipinski's rules broken 0

Generated using the Chemistry Development Kit (CDK) (Willighagen EL et al. Journal of Cheminformatics vol. 9:33. 2017, doi:10.1186/s13321-017-0220-4; https://cdk.github.io/)
SMILES / InChI / InChIKey
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SMILES / InChI / InChIKey

SMILES (Simplified Molecular Input Line Entry Specification) A specification for unambiguously describing the structure of chemical molecules using short ASCII strings. Canonical SMILES specify a unique representation of the 2D structure without chiral or isotopic specifications. Isomeric SMILES include chiral specification and isotopes.

Standard InChI (IUPAC International Chemical Identifier) and InChIKey InChI is a non-proprietary, standard, textual identifier for chemical substances designed to facilitate linking of information and database searching. An InChIKey is a simplified version of a full InChI, designed for easier web searching.

Generated using the Chemistry Development Kit (CDK) (Willighagen EL et al. Journal of Cheminformatics vol. 9:33. 2017, doi:10.1186/s13321-017-0220-4; https://cdk.github.io/)

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Canonical SMILES OC(=O)CCC(C(=O)O)N
Isomeric SMILES OC(=O)CC[C@@H](C(=O)O)N
InChI InChI=1S/C5H9NO4/c6-3(5(9)10)1-2-4(7)8/h3H,1-2,6H2,(H,7,8)(H,9,10)/t3-/m0/s1
InChI Key WHUUTDBJXJRKMK-VKHMYHEASA-N

Generated using the Chemistry Development Kit (CDK) (Willighagen EL et al. Journal of Cheminformatics vol. 9:33. 2017, doi:10.1186/s13321-017-0220-4; https://cdk.github.io/)
Bioactivity Comments
Glutamate has been described as a coagonist along with glycine at NMDA receptors [4].
Natural/Endogenous Targets
Target
GluA1
GluA2
GluA3
GluA4
GluD1
GluD2
GluK1
GluK2
GluK3
GluK4
GluK5
GluN1
GluN2A
GluN2B
GluN2C
GluN2D
GluN3A
GluN3B
mGlu1 receptor
mGlu2 receptor
mGlu3 receptor
mGlu4 receptor
mGlu5 receptor
mGlu6 receptor
mGlu7 receptor
mGlu8 receptor
Enzymes Catalysing Reactions with this Compound as a Substrate or Product
Enzyme EC number Reaction Reference
Glutamic acid decarboxylase 1 4.1.1.15 L-glutamic acid + H+ -> GABA + CO2
Glutamic acid decarboxylase 2 4.1.1.15 L-glutamic acid + H+ -> GABA + CO2
4-aminobutyrate aminotransferase 2.6.1.19, 2.6.1.22 GABA + α-ketoglutaric acid = L-glutamic acid + 4-oxobutanoate

(S)-3-amino-2-methylpropanoate + α-ketoglutaric acid = 2-methyl-3-oxopropanoate + L-glutamic acid
Tyrosine aminotransferase 2.6.1.5 L-tyrosine + α-ketoglutaric acid -> 4-hydroxyphenylpyruvic acid + L-glutamic acid
Transporters Moving this Compound Across a Lipid Membrane
Transporter EC number Reaction Reference
Excitatory amino acid transporter 1
Excitatory amino acid transporter 2
Excitatory amino acid transporter 3
Excitatory amino acid transporter 4
Excitatory amino acid transporter 5
Cation-chloride cotransporter 9
Sialin 13
AGC1
AGC2
Mitochondrial glutamate carrier 2
Mitochondrial glutamate carrier 1
Alanine/serine/cysteine transporter 2
Vesicular glutamate transporter 1
Vesicular glutamate transporter 2
Vesicular glutamate transporter 3
SLC26A7
SLC26A9
Sodium-coupled neutral amino acid transporter 3 7
Selectivity at GPCRs
Key to terms and symbols Click column headers to sort
Target Sp. Type Action Value Parameter Concentration range (M) Reference
mGlu3 receptor Ligand is endogenous in the given species Hs Agonist Full agonist 7.4 pKi - 9
⤷ pKi 7.4 [9]
mGlu1 receptor Ligand is endogenous in the given species Rn Agonist Full agonist 6.4 – 6.5 pKi - 11,14
⤷ pKi 6.4 – 6.5 [11,14]
mGlu3 receptor Ligand is endogenous in the given species Rn Agonist Full agonist 6.4 pKi - 16
⤷ pKi 6.4 [16]
mGlu2 receptor Ligand is endogenous in the given species Rn Agonist Full agonist 5.4 – 5.9 pKi - 2,6
⤷ pKi 5.4 – 5.9 [2,6]
mGlu4 receptor Ligand is endogenous in the given species Rn Agonist Full agonist 4.9 – 5.5 pKi - 1,8,17-18
⤷ pKi 4.9 – 5.5 [1,8,17-18]
mGlu2 receptor Ligand is endogenous in the given species Hs Agonist Full agonist 4.9 pKi - 9
⤷ pKi 4.9 [9]
mGlu7 receptor Ligand is endogenous in the given species Hs Agonist Full agonist 3.1 pKi - 19
⤷ pKi 3.1 [19]
mGlu3 receptor Ligand is endogenous in the given species Hs Agonist Agonist 5.3 – 5.4 pEC50 - 15
⤷ pEC50 5.3 – 5.4 [15]
mGlu5 receptor Ligand is endogenous in the given species Hs Agonist Agonist 5.0 – 5.5 pEC50 - 15
⤷ pEC50 5.0 – 5.5 [15]
mGlu8 receptor Ligand is endogenous in the given species Hs Agonist Agonist 4.9 – 5.6 pEC50 - 15
⤷ pEC50 4.9 – 5.6 [15]
mGlu6 receptor Ligand is endogenous in the given species Hs Agonist Full agonist 5.2 pEC50 - 10
⤷ pEC50 5.2 [10]
mGlu4 receptor Ligand is endogenous in the given species Hs Agonist Agonist 4.7 – 5.5 pEC50 - 15
⤷ pEC50 4.7 – 5.5 [15]
mGlu2 receptor Ligand is endogenous in the given species Hs Agonist Agonist 4.7 – 5.4 pEC50 - 15
⤷ pEC50 4.7 – 5.4 [15]
mGlu1 receptor Ligand is endogenous in the given species Hs Agonist Agonist 4.8 – 5.0 pEC50 - 15
⤷ pEC50 4.8 – 5.0 [15]
mGlu6 receptor Ligand is endogenous in the given species Hs Agonist Agonist 4.8 pEC50 - 15
⤷ pEC50 4.8 [15]
mGlu6 receptor Ligand is endogenous in the given species Rn Agonist Full agonist 4.4 pEC50 - 3
⤷ pEC50 4.4 [3]
mGlu7 receptor Ligand is endogenous in the given species Hs Agonist Agonist 3.0 pEC50 - 15
⤷ pEC50 3.0 [15]
mGlu5 receptor Ligand is endogenous in the given species Rn Agonist Full agonist 6.1 pIC50 - 14
⤷ pIC50 6.1 [14]
mGlu8 receptor Ligand is endogenous in the given species Hs Agonist Full agonist 5.0 – 5.7 pIC50 - 12,20
⤷ pIC50 5.0 – 5.7 [12,20]
Additional information and targets (data relate to human unless otherwise stated)
Description Data Reference
Endogenous substrates at Alanine/serine/cysteine transporter 2 L-alanine = L-serine = L-cysteine (low Vmax) = L-threonine = L-glutamine = L-asparagine >> L-methionine ≅ glycine ≅ L-leucine > L-valine > L-glutamic acid (enhanced at low pH)
Endogenous substrates at Vesicular glutamate transporter 1 L-glutamic acid > D-glutamic acid
Endogenous substrates at Vesicular glutamate transporter 2 L-glutamic acid > D-glutamic acid
Endogenous substrates at Vesicular glutamate transporter 3 L-glutamic acid > D-glutamic acid
Substrates at Sodium-coupled neutral amino acid transporter 3 L-histidine , L-glutamine > L-asparagine, L-alanine > L-glutamic acid 7
Amino-acid rank order of potency at CaS receptor L-phenylalanine, L-tryptophan, L-histidine > L-alanine > L-serine, L-proline, L-glutamic acid > L-aspartic acid (not L-lysine, L-arginine, L-leucine and L-isoleucine) 5
Substrates at SLC26A9 I- > Br- > NO3- > Cl- > L-glutamic acid
Substrates at SLC26A7 NO3- >> Cl- = Br- = I- > SO42- = L-glutamic acid
Targets where the ligand is described in the comment field
Target Comment
Folate hydrolase (prostate-specific membrane antigen) 1 Folate hydrolase is also known as NAALADase as it is responsible for the hydrolysis of N-acetaspartylglutamate to form N-acetylaspartate and L-glutamate (L-glutamic acid). In the gut, the enzyme assists in the assimilation of folate by hydrolysing dietary poly-gamma-glutamylfolate. The enzyme is highly expressed in the prostate, and its expression is up-regulated in cancerous tissue. A tagged version of the antibody capromab has been used for imaging purposes.
Ligand mentioned in the following text fields
Metabotropic glutamate receptors overview
SLC17 phosphate and organic anion transporter family overview
Taste 1 receptors overview
SLC7 family comments