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Revisiting VH1 phosphatase at the time of monkeypox: back to the spotlight.
Bottini, Angel; Pacheco, Diana R D C G; Forti, Fabio L; Bottini, Nunzio.
Afiliación
  • Bottini A; Department of Medicine, Cedars-Sinai Medical Center, Los Angeles, CA, U.S.A.
  • Pacheco DRDCG; Department of Biochemistry, Institute of Chemistry, University of Sao Paulo, Sao Paulo, SP, Brazil.
  • Forti FL; Department of Biochemistry, Institute of Chemistry, University of Sao Paulo, Sao Paulo, SP, Brazil.
  • Bottini N; Department of Medicine, Cedars-Sinai Medical Center, Los Angeles, CA, U.S.A.
Biochem Soc Trans ; 51(4): 1419-1427, 2023 08 31.
Article en En | MEDLINE | ID: mdl-37409507
ABSTRACT
Vaccinia virus is a poxvirus that has been successfully leveraged to develop vaccines for smallpox, which is caused by the closely related Variola virus. Smallpox has been declared as 'eradicated' by the WHO in 1980; however, it still poses a potential bioterrorism threat. More recently, the spreading of monkeypox (MPox) in non-endemic countries has further highlighted the importance of continuing the exploration for druggable targets for poxvirus infections. The vaccinia H1 (VH1) phosphatase is the first reported dual specificity phosphatase (DUSP) able to hydrolyze both phosphotyrosine and phosphoserine/phosphotheonine residues. VH1 is a 20 kDa protein that forms a stable dimer and can dephosphorylate both viral and cellular substrates to regulate the viral replication cycle and host immune response. VH1 dimers adopt a domain swap mechanism with the first 20 amino acids of each monomer involved in dense electrostatic interaction and salt bridge formations while hydrophobic interactions between the N-terminal and C-terminal helices further stabilize the dimer. VH1 appears to be an ideal candidate for discovery of novel anti-poxvirus agents because it is highly conserved within the poxviridae family and is a virulence factor, yet it displays significant divergence in sequence and dimerization mechanism from its human closest ortholog vaccinia H1-related (VHR) phosphatase, encoded by the DUSP3 gene. As the dimeric quaternary structure of VH1 is essential for its phosphatase activity, strategies leading to disruption of the dimer structure might aid in VH1 inhibitor development.
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Texto completo: 1 Banco de datos: MEDLINE Asunto principal: Vaccinia / Viruela / Mpox Límite: Humans Idioma: En Revista: Biochem Soc Trans Año: 2023 Tipo del documento: Article País de afiliación: Estados Unidos

Texto completo: 1 Banco de datos: MEDLINE Asunto principal: Vaccinia / Viruela / Mpox Límite: Humans Idioma: En Revista: Biochem Soc Trans Año: 2023 Tipo del documento: Article País de afiliación: Estados Unidos