Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 1 de 1
Filtrar
Mais filtros

Base de dados
Ano de publicação
Tipo de documento
Intervalo de ano de publicação
1.
Proc Natl Acad Sci U S A ; 119(39): e2210908119, 2022 09 27.
Artigo em Inglês | MEDLINE | ID: mdl-36122239

RESUMO

Chlamydia protein associating with death domains (CADD) is involved in the biosynthesis of para-aminobenzoate (pABA), an essential component of the folate cofactor that is required for the survival and proliferation of the human pathogen Chlamydia trachomatis. The pathway used by Chlamydiae for pABA synthesis differs from the canonical multi-enzyme pathway used by most bacteria that relies on chorismate as a metabolic precursor. Rather, recent work showed pABA formation by CADD derives from l-tyrosine. As a member of the emerging superfamily of heme oxygenase-like diiron oxidases (HDOs), CADD was proposed to use a diiron cofactor for catalysis. However, we report maximal pABA formation by CADD occurs upon the addition of both iron and manganese, which implicates a heterobimetallic Fe:Mn cluster is the catalytically active form. Isotopic labeling experiments and proteomics studies show that CADD generates pABA from a protein-derived tyrosine (Tyr27), a residue that is ∼14 Šfrom the dimetal site. We propose that this self-sacrificial reaction occurs through O2 activation by a probable Fe:Mn cluster through a radical relay mechanism that connects to the "substrate" Tyr, followed by amination and direct oxygen insertion. These results provide the molecular basis for pABA formation in C. trachomatis, which will inform the design of novel therapeutics.


Assuntos
Proteínas de Bactérias , Chlamydia trachomatis , Oxigenases , Tirosina , para-Aminobenzoatos , Proteínas de Bactérias/metabolismo , Chlamydia trachomatis/enzimologia , Ácido Fólico , Ferro/metabolismo , Manganês/metabolismo , Oxigênio/metabolismo , Oxigenases/metabolismo , Tirosina/metabolismo , para-Aminobenzoatos/metabolismo
SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA