[English] 日本語
![](img/lk-miru.gif)
- PDB-8jy8: Structure of TbAQP2 in complex with anti-trypanosomatid drug pent... -
+
Open data
-
Basic information
Entry | Database: PDB / ID: 8jy8 | ||||||
---|---|---|---|---|---|---|---|
Title | Structure of TbAQP2 in complex with anti-trypanosomatid drug pentamidine | ||||||
![]() | Aquaglyceroporin 2 | ||||||
![]() | MEMBRANE PROTEIN / Aquaporin | ||||||
Function / homology | glycerol channel activity / urea transmembrane transporter activity / water channel activity / Major intrinsic protein / Major intrinsic protein / Aquaporin-like / membrane / 1,5-BIS(4-AMIDINOPHENOXY)PENTANE / Aquaglyceroporin 2![]() | ||||||
Biological species | ![]() ![]() | ||||||
Method | ELECTRON MICROSCOPY / single particle reconstruction / cryo EM / Resolution: 2.45 Å | ||||||
![]() | Chen, W. / Wang, C. | ||||||
Funding support | ![]()
| ||||||
![]() | ![]() Title: Structural insights into drug transport by an aquaglyceroporin. Authors: Wanbiao Chen / Rongfeng Zou / Yi Mei / Jiawei Li / Yumi Xuan / Bing Cui / Junjie Zou / Juncheng Wang / Shaoquan Lin / Zhe Zhang / Chongyuan Wang / ![]() Abstract: Pentamidine and melarsoprol are primary drugs used to treat the lethal human sleeping sickness caused by the parasite Trypanosoma brucei. Cross-resistance to these two drugs has recently been linked ...Pentamidine and melarsoprol are primary drugs used to treat the lethal human sleeping sickness caused by the parasite Trypanosoma brucei. Cross-resistance to these two drugs has recently been linked to aquaglyceroporin 2 of the trypanosome (TbAQP2). TbAQP2 is the first member of the aquaporin family described as capable of drug transport; however, the underlying mechanism remains unclear. Here, we present cryo-electron microscopy structures of TbAQP2 bound to pentamidine or melarsoprol. Our structural studies, together with the molecular dynamic simulations, reveal the mechanisms shaping substrate specificity and drug permeation. Multiple amino acids in TbAQP2, near the extracellular entrance and inside the pore, create an expanded conducting tunnel, sterically and energetically allowing the permeation of pentamidine and melarsoprol. Our study elucidates the mechanism of drug transport by TbAQP2, providing valuable insights to inform the design of drugs against trypanosomiasis. | ||||||
History |
|
-
Structure visualization
Structure viewer | Molecule: ![]() ![]() |
---|
-
Downloads & links
-
Download
PDBx/mmCIF format | ![]() | 167.9 KB | Display | ![]() |
---|---|---|---|---|
PDB format | ![]() | 134.5 KB | Display | ![]() |
PDBx/mmJSON format | ![]() | Tree view | ![]() | |
Others | ![]() |
-Validation report
Summary document | ![]() | 1.1 MB | Display | ![]() |
---|---|---|---|---|
Full document | ![]() | 1.1 MB | Display | |
Data in XML | ![]() | 37.7 KB | Display | |
Data in CIF | ![]() | 49.8 KB | Display | |
Arichive directory | ![]() ![]() | HTTPS FTP |
-Related structure data
Related structure data | ![]() 36723MC ![]() 8jy6C ![]() 8jy7C M: map data used to model this data C: citing same article ( |
---|---|
Similar structure data | Similarity search - Function & homology ![]() |
-
Links
-
Assembly
Deposited unit | ![]()
|
---|---|
1 |
|
-
Components
#1: Protein | Mass: 33614.645 Da / Num. of mol.: 4 Source method: isolated from a genetically manipulated source Source: (gene. exp.) ![]() ![]() ![]() #2: Chemical | ChemComp-PNT / Has ligand of interest | Y | |
---|
-Experimental details
-Experiment
Experiment | Method: ELECTRON MICROSCOPY |
---|---|
EM experiment | Aggregation state: PARTICLE / 3D reconstruction method: single particle reconstruction |
-
Sample preparation
Component | Name: TbAQP2 complex with pentamidine / Type: COMPLEX / Entity ID: #1 / Source: RECOMBINANT |
---|---|
Source (natural) | Organism: ![]() ![]() |
Source (recombinant) | Organism: ![]() |
Buffer solution | pH: 7.5 |
Specimen | Embedding applied: NO / Shadowing applied: NO / Staining applied: NO / Vitrification applied: YES |
Vitrification | Cryogen name: ETHANE / Humidity: 100 % |
-
Electron microscopy imaging
Experimental equipment | ![]() Model: Titan Krios / Image courtesy: FEI Company |
---|---|
Microscopy | Model: FEI TITAN KRIOS |
Electron gun | Electron source: ![]() |
Electron lens | Mode: BRIGHT FIELD / Nominal defocus max: 3000 nm / Nominal defocus min: 800 nm |
Image recording | Electron dose: 71 e/Å2 / Film or detector model: GATAN K3 (6k x 4k) |
-
Processing
EM software |
| ||||||||||||||||||||||||
---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
CTF correction | Type: NONE | ||||||||||||||||||||||||
3D reconstruction | Resolution: 2.45 Å / Resolution method: FSC 0.143 CUT-OFF / Num. of particles: 539330 / Symmetry type: POINT | ||||||||||||||||||||||||
Refine LS restraints |
|