5HTP aptamer

•



Description

In 2017, Batey, R. T. et al. exploits the secondary and tertiary structural architecture of naturally evolved riboswitches and ribozymes to scaffold small molecule binding pockets raised through in vitro selection. This method was applied to neurotransmitter precursors 5-hydroxytryptophan and 3,4-dihydroxyphenylalanine, yielding aptamers that are easy to recognize and characterize. Additionally, nucleic acid sensing devices were designed to function both in vitro and in cellular environments. Moreover, the crystal structure of the complex between 5-hydroxytryptophan and the selected aptamer was resolved at a resolution of 2 Å using X-ray crystallography[1].



SELEX

Batey, R. T. et al. used RNA libraries constructed on the basis of three different riboswitch and ribozyme backbones that include the xpt-pbuX guanine riboswitch from Bacillus subtilis, the Vc2 cyclic di-guanosine riboswitch from Vibrio cholerae, and the Schistosoma mansoni's hammerhead ribozyme. After seven rounds of screening, and through these screening rounds, RNA aptamers were identified that were able to specifically bind 5HTP. By this method, and in particular by using the GR backbone, it was possible to screen for at least three major families of RNA aptamers, designated 5GR-I, 5GR-II, and 5GR-III, respectively.They determined the consensus secondary structures of six major clusters from the two selections against 5HTP[1].

Detailed information are accessible on SELEX page.



Structure

2D representation

Here we used ribodraw to complete the figure, through the 3D structure information. The 5GR-II RNA aptamer was named by Batey, R. T. et al. in the article[1].

5'-GGACACUGAUGAUCGCGUGGAUAUGGCACGCAUUGAAUUGUUGGACACCGUAAAUGUCCUAACACGUGUCC-3'

drawing

3D visualisation

Batey, R. T. et al. obtained the structure of the 5HTP aptamer by X-ray crystallography, which was obtained after screening based on the in vitro selection of three-dimensional structurally important points (SELEX) method. This structure shows details of 5HTP binding to the RNA aptamer, including the 3D structure of the RNA and details of the interaction with 5HTP. The resolution of this structure is 2.0 Å. In the structure, 5HTP is localized in the three-dimensional junction structure of RNA, with which it hydrogen bonds and stacking interactions mainly through nucleotides in the J2/3 region. In addition, the recognition of 5HTP interacts with a specific T-loop in the RNA structure, which is essential for the high affinity and specific binding of 5HTP.The PDB ID of this structure is 5KPY[1].

Additional available structures that have been solved and detailed information are accessible on Structures page.

(Clicking the "Settings/Controls info" to turn Spin off)      

drawing PDBe Molstar




Binding pocket

Left: Surface representation of the binding pocket of the aptamer generated from PDB ID: 5KPY by X-ray crystallography. 5-HTP (shown in sticks) is labeled in magenta. Right: The hydrogen bonds of binding sites of the aptamer bound with 5HTP.

drawing drawing


Ligand information

SELEX ligand

Batey, R. T. et al. used isothermal titration calorimetry (ITC) to determine the binding affinity and specificity between 5-HTP and 5GR-II RNA Aptamers. This method accurately measures the amount of heat absorbed or released during the binding process to derive dissociation constants. The specificity of this RNA was quantified by elution with 5HTP, L-tryptophan, Serotonin (5-HT) and α-methyl 5-hydroxy-L-tryptophan (Me-5HTP)[1].

drawing

Structure ligand

5-hydroxytryptophan is a tryptophan derivative that is tryptophan substituted by a hydroxy group at position 5. It has a role as a human metabolite and a neurotransmitter.-----From Pubchem

PubChem CID: a unique identifier for substances in the PubChem database.

CAS number: a global registry number for chemical substances.

Drugbank: a comprehensive database with detailed information on drugs and drug targets.

Name PubChem CID Molecular Formula Molecular Weight CAS Solubility Drugbank ID
5-hydroxytryptophan (5HTP) 144 C11H12N2O3 220.22 g/mol 56-69-9 12.5 mg/mL DB02959
drawing drawing

Similar compound

We screened the compounds with great similarity to 5HTP by using the ZINC database and showed some of the compounds' structure diagrams. For some CAS numbers not available,we will supplement them with Pubchem CID.

ZINC ID: a compound identifier used by the ZINC database, one of the largest repositories for virtual screening of drug-like molecules.

PubChem CID: a unique identifier for substances in the PubChem database.

CAS number: a global registry number for chemical substances.

ZINC ID Name CAS Pubchem CID Structure
ZINC000000083315 Tryptophan 73-22-3 6305 drawing
ZINC000000057156 5-Fluorotryptophan 154-08-5 9577 drawing
ZINC000003651522 Hyrtioerectine C NA 11506813 drawing
ZINC000006045354 5-Amino-DL-tryptophan 6383-69-3 4018454 drawing
ZINC000000391257 5-Methyl-DL-tryptophan 951-55-3 92852 drawing
ZINC000000057131 5-Bromo-DL-tryptophan 6548-09-0 96735 drawing
ZINC000002572392 2-amino-3-(5-chloro-1H-indol-3-yl)propanoic acid 154-07-4 596210 drawing
ZINC000000057157 5-Fluoro-d-tryptophan 97749-24-1 688358 drawing


References

[1] Recurrent RNA motifs as scaffolds for genetically encodable small-molecule biosensors.
Porter EB, Polaski JT, Morck MM, Batey RT
Nature chemical biology. 2017 Mar;13(3):295-301. (2017)