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

Departament de Pediatria, d’Obstetrícia i Ginecologia i de Medicina Preventiva i Salut Pública

Producció científica: Contribució a revista › Article › Recerca

10 Cites (Scopus)

Resum

© 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.

Idioma original	Anglès
Pàgines (de-a)	2510-2517
Revista	ACS Chemical Neuroscience
Volum	10
DOIs	https://doi.org/10.1021/acschemneuro.9b00019
Estat de la publicació	Publicada - 15 de maig 2019

Accés al document

10.1021/acschemneuro.9b00019

Altres arxius i enllaços

Com citar-ho

@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",

publisher = "American Chemical Society",

}

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

UR - http://www.mendeley.com/research/inhibition-alanineserinecysteine1-transporter-bms466442

UR - https://www.scopus.com/pages/publications/85063130599

U2 - 10.1021/acschemneuro.9b00019

DO - 10.1021/acschemneuro.9b00019

M3 - Article

C2 - 30821959

SN - 1948-7193

VL - 10

SP - 2510

EP - 2517

JO - ACS Chemical Neuroscience

JF - ACS Chemical Neuroscience

ER -

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

Resum

Accés al document

Altres arxius i enllaços

Fingerprint

Com citar-ho