Inhibition of the Alanine-Serine-Cysteine-1 Transporter by BMS-466442

Ivan R. Torrecillas; Susana Conde-Ceide; Ana Isabel De Lucas; Aránzazu Garcĺa Molina; Andrés A. Trabanco; Hilde Lavreysen; Leonardo Pardo; Gary Tresadern

doi:10.1021/acschemneuro.9b00019

Inhibition of the Alanine-Serine-Cysteine-1 Transporter by BMS-466442

Ivan R. Torrecillas, Susana Conde-Ceide, Ana Isabel De Lucas, Aránzazu Garcĺa Molina, Andrés A. Trabanco, Hilde Lavreysen, Leonardo Pardo, Gary Tresadern

Research output: Contribution to journal › Article › Research

1 Citation (Scopus)

Abstract

© 2019 American Chemical Society. Experiment and modeling were combined to understand inhibition of the alanine-serine-cysteine-1 (asc1) transporter. The structure-activity relationship (SAR) was explored with synthesis of analogues of BMS-466442. Direct target interaction and binding site location between TM helices 6 and 10 were confirmed via site directed mutagenesis. Computational modeling suggested the inhibitor binds via competitive occupation of the orthosteric site while also blocking the movement of TM helices that are required for transport.

Original language	English
Pages (from-to)	2510-2517
Journal	ACS Chemical Neuroscience
Volume	10
DOIs	https://doi.org/10.1021/acschemneuro.9b00019
Publication status	Published - 15 May 2019

Keywords

asc1
binding mode
homology model
mutagenesis
SDM
SLC7A10.
transporter

Access to Document

10.1021/acschemneuro.9b00019

Fingerprint Dive into the research topics of 'Inhibition of the Alanine-Serine-Cysteine-1 Transporter by BMS-466442'. Together they form a unique fingerprint.

Cite this

@article{caae2e6e5fac4ed7864301c2074b880c,

title = "Inhibition of the Alanine-Serine-Cysteine-1 Transporter by BMS-466442",

abstract = "{\textcopyright} 2019 American Chemical Society. Experiment and modeling were combined to understand inhibition of the alanine-serine-cysteine-1 (asc1) transporter. The structure-activity relationship (SAR) was explored with synthesis of analogues of BMS-466442. Direct target interaction and binding site location between TM helices 6 and 10 were confirmed via site directed mutagenesis. Computational modeling suggested the inhibitor binds via competitive occupation of the orthosteric site while also blocking the movement of TM helices that are required for transport.",

keywords = "asc1, binding mode, homology model, mutagenesis, SDM, SLC7A10., transporter",

author = "Torrecillas, {Ivan R.} and Susana Conde-Ceide and {De Lucas}, {Ana Isabel} and {Garc{\'l}a Molina}, Ar{\'a}nzazu and Trabanco, {Andr{\'e}s A.} and Hilde Lavreysen and Leonardo Pardo and Gary Tresadern",

year = "2019",

month = may,

day = "15",

doi = "10.1021/acschemneuro.9b00019",

language = "English",

volume = "10",

pages = "2510--2517",

journal = "ACS Chemical Neuroscience",

issn = "1948-7193",

}

TY - JOUR

T1 - Inhibition of the Alanine-Serine-Cysteine-1 Transporter by BMS-466442

AU - Torrecillas, Ivan R.

AU - Conde-Ceide, Susana

AU - De Lucas, Ana Isabel

AU - Garcĺa Molina, Aránzazu

AU - Trabanco, Andrés A.

AU - Lavreysen, Hilde

AU - Pardo, Leonardo

AU - Tresadern, Gary

PY - 2019/5/15

Y1 - 2019/5/15

N2 - © 2019 American Chemical Society. Experiment and modeling were combined to understand inhibition of the alanine-serine-cysteine-1 (asc1) transporter. The structure-activity relationship (SAR) was explored with synthesis of analogues of BMS-466442. Direct target interaction and binding site location between TM helices 6 and 10 were confirmed via site directed mutagenesis. Computational modeling suggested the inhibitor binds via competitive occupation of the orthosteric site while also blocking the movement of TM helices that are required for transport.

AB - © 2019 American Chemical Society. Experiment and modeling were combined to understand inhibition of the alanine-serine-cysteine-1 (asc1) transporter. The structure-activity relationship (SAR) was explored with synthesis of analogues of BMS-466442. Direct target interaction and binding site location between TM helices 6 and 10 were confirmed via site directed mutagenesis. Computational modeling suggested the inhibitor binds via competitive occupation of the orthosteric site while also blocking the movement of TM helices that are required for transport.

KW - asc1

KW - binding mode

KW - homology model

KW - mutagenesis

KW - SDM

KW - SLC7A10.

KW - transporter

U2 - 10.1021/acschemneuro.9b00019

DO - 10.1021/acschemneuro.9b00019

M3 - Article

C2 - 30821959

VL - 10

SP - 2510

EP - 2517

JO - ACS Chemical Neuroscience

JF - ACS Chemical Neuroscience

SN - 1948-7193

ER -