Covalent inhibition of hAChE by organophosphates causes homodimer dissociation through long-range allosteric effects.

Blumenthal, Donald K; Cheng, Xiaolin; Fajer, Mikolai; Ho, Kwok-Yiu; Rohrer, Jacqueline; Gerlits, Oksana; Taylor, Palmer; Juneja, Puneet; Kovalevsky, Andrey; Radic, Zoran

Blumenthal, Donald K; Cheng, Xiaolin; Fajer, Mikolai; Ho, Kwok-Yiu; Rohrer, Jacqueline; Gerlits, Oksana; Taylor, Palmer; Juneja, Puneet; Kovalevsky, Andrey; Radic, Zoran.

Afiliação

Blumenthal DK; Department of Pharmacology and Toxicology, University of Utah, Salt Lake City, Utah, USA.
Cheng X; Division of Medicinal Chemistry & Pharmacognosy, College of Pharmacy, The Ohio State University, Columbus, Ohio, USA.
Fajer M; Division of Medicinal Chemistry & Pharmacognosy, College of Pharmacy, The Ohio State University, Columbus, Ohio, USA.
Ho KY; Skaggs School of Pharmacy and Pharmaceutical Sciences, UC San Diego, La Jolla, California, USA.
Rohrer J; Skaggs School of Pharmacy and Pharmaceutical Sciences, UC San Diego, La Jolla, California, USA.
Gerlits O; Department of Natural Sciences, Tennessee Wesleyan University, Athens, Tennessee, USA.
Taylor P; Skaggs School of Pharmacy and Pharmaceutical Sciences, UC San Diego, La Jolla, California, USA.
Juneja P; Cryo-EM Facility, Iowa State University, Ames, Iowa, USA.
Kovalevsky A; Neutron Scattering Division, Oak Ridge National Laboratory, Oak Ridge, Tennessee, USA.
Radic Z; Skaggs School of Pharmacy and Pharmaceutical Sciences, UC San Diego, La Jolla, California, USA. Electronic address: zradic@ucsd.edu.

J Biol Chem ; 297(3): 101007, 2021 09.

Article em En | MEDLINE | ID: mdl-34324828

Assuntos

Acetilcolinesterase/efeitos dos fármacos; Inibidores da Colinesterase/farmacologia; Organofosfatos/farmacologia; Acetilcolinesterase/química; Acetilcolinesterase/metabolismo; Regulação Alostérica; Domínio Catalítico; Cromatografia em Gel; Microscopia Crioeletrônica; Dimerização; Eletroforese em Gel de Poliacrilamida; Células HEK293; Humanos; Fosforilação; Espalhamento a Baixo Ângulo; Estereoisomerismo; Difração de Raios X

Palavras-chave

4-helix bundle; SAXS; acetylcholinesterase; allosteric behavior; enzyme structure; molecular dynamics; organophosphate intoxication; oxime reactivation; paraoxon; small-angle X-ray scattering; structurefunction

Texto completo

Imprimir

XML

PubMed Links

Buscar no Google

Texto completo: 1 Base de dados: MEDLINE Assunto principal: Organofosfatos / Acetilcolinesterase / Inibidores da Colinesterase Idioma: En Ano de publicação: 2021 Tipo de documento: Article

Texto completo

Imprimir

XML

PubMed Links

Buscar no Google