PDBsum entry 4pda

Transport protein

PDB id: 4pda

Contents

Protein chain

404 a.a.

Ligands

CTN

DMU

Metals

_NA

Waters ×28

PDB id:

4pda

Name:

Transport protein

Title:

Structure of vccnt-7c8c bound to cytidine

Structure:

Nupc family protein. Chain: a. Engineered: yes. Mutation: yes

Source:

Vibrio cholerae serotype o1. Organism_taxid: 243277. Strain: atcc 39315 / el tor inaba n16961. Gene: vc_2352. Expressed in: escherichia coli. Expression_system_taxid: 562.

Resolution:

2.61Å R-factor: 0.215 R-free: 0.239

Authors:

Z.L.Johnson,S.-Y.Lee

Key ref:

Z.L.Johnson et al. (2014). Structural basis of nucleoside and nucleoside drug selectivity by concentrative nucleoside transporters. Elife, 3, e03604. PubMed id: 25082345 DOI: 10.7554/eLife.03604

Date:

17-Apr-14 Release date: 13-Aug-14

Protein chain

Q9KPL5  (Q9KPL5_VIBCH) -  Nucleoside permease from Vibrio cholerae serotype O1 (strain ATCC 39315 / El Tor Inaba N16961)

Seq: 418 a.a.

Struc: 404 a.a.*

* PDB and UniProt seqs differ at 2 residue positions (black crosses)

DOI no: 10.7554/eLife.03604

Elife 3:e03604 (2014)

PubMed id: 25082345

Structural basis of nucleoside and nucleoside drug selectivity by concentrative nucleoside transporters.

Z.L.Johnson, J.H.Lee, K.Lee, M.Lee, D.Y.Kwon, J.Hong, S.Y.Lee.

ABSTRACT

Concentrative nucleoside transporters (CNTs) are responsible for cellular entry of nucleosides, which serve as precursors to nucleic acids and act as signaling molecules. CNTs also play a crucial role in the uptake of nucleoside-derived drugs, including anticancer and antiviral agents. Understanding how CNTs recognize and import their substrates could not only lead to a better understanding of nucleoside-related biological processes but also the design of nucleoside-derived drugs that can better reach their targets. Here, we present a combination of X-ray crystallographic and equilibrium-binding studies probing the molecular origins of nucleoside and nucleoside drug selectivity of a CNT from Vibrio cholerae. We then used this information in chemically modifying an anticancer drug so that it is better transported by and selective for a single human CNT subtype. This work provides proof of principle for utilizing transporter structural and functional information for the design of compounds that enter cells more efficiently and selectively.DOI: http://dx.doi.org/10.7554/eLife.03604.001.