Pdr5: A master of asymmetry.
Drug Resist Updat
; 71: 101010, 2023 Nov.
Article
em En
| MEDLINE
| ID: mdl-37862721
ABSTRACT
Pdr5 is a founding member of a large (pdr) subfamily of clinically and agriculturally significant fungal ABC transporters. The tremendous power of yeast genetics combined with biochemical and structural approaches revealed the astonishing asymmetry of this efflux pump. Asymmetry is manifested in Pdr5's ATP-binding sites, drug binding sites, signal transformation interface, and molecular exit gate. Even its mode of conformational switching is asymmetric with one half of the protein remaining nearly stationary. In the case of its ATP-binding sites, asymmetry is created by replacing a set of highly conserved residues with a characteristic set of deviant ones. This contrasts with the asymmetry of the molecular gate. There, a full complement of canonical residues is present, but structural features in the vicinity prevent some of these from forming a molecular plug during closure. Compared to their canonical-functioning counterparts, the deviant ATP site and these gating residues have different, essential functions. In addition to its remarkable asymmetry, the surprising observation that Pdr5 is a drug / proton co-transporter shines a new light on this remarkable protein.
Palavras-chave
Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
Trifosfato de Adenosina
/
Transportadores de Cassetes de Ligação de ATP
Limite:
Humans
Idioma:
En
Revista:
Drug Resist Updat
Assunto da revista:
ANTINEOPLASICOS
Ano de publicação:
2023
Tipo de documento:
Article