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Structural and Biochemical Analysis of Protein-Protein Interactions Between the Acyl-Carrier Protein and Product Template Domain.
Barajas, Jesus F; Finzel, Kara; Valentic, Timothy R; Shakya, Gaurav; Gamarra, Nathan; Martinez, Delsy; Meier, Jordan L; Vagstad, Anna L; Newman, Adam G; Townsend, Craig A; Burkart, Michael D; Tsai, Shiou-Chuan.
Afiliação
  • Barajas JF; Department of Molecular Biology and Biochemistry, Chemistry, and Pharmaceutical Sciences, University of California, Irvine, Irvine, CA, 92697, USA.
  • Finzel K; Department of Chemistry and Biochemistry, University of California, San Diego, La Jolla, CA, 92093, USA.
  • Valentic TR; Department of Molecular Biology and Biochemistry, Chemistry, and Pharmaceutical Sciences, University of California, Irvine, Irvine, CA, 92697, USA.
  • Shakya G; Department of Molecular Biology and Biochemistry, Chemistry, and Pharmaceutical Sciences, University of California, Irvine, Irvine, CA, 92697, USA.
  • Gamarra N; Department of Molecular Biology and Biochemistry, Chemistry, and Pharmaceutical Sciences, University of California, Irvine, Irvine, CA, 92697, USA.
  • Martinez D; Department of Molecular Biology and Biochemistry, Chemistry, and Pharmaceutical Sciences, University of California, Irvine, Irvine, CA, 92697, USA.
  • Meier JL; Department of Chemistry and Biochemistry, University of California, San Diego, La Jolla, CA, 92093, USA.
  • Vagstad AL; Department of Chemistry, The Johns Hopkins University, 3400 North Charles Street, Baltimore, MD, 21218, USA.
  • Newman AG; Department of Chemistry, The Johns Hopkins University, 3400 North Charles Street, Baltimore, MD, 21218, USA.
  • Townsend CA; Department of Chemistry, The Johns Hopkins University, 3400 North Charles Street, Baltimore, MD, 21218, USA.
  • Burkart MD; Department of Chemistry and Biochemistry, University of California, San Diego, La Jolla, CA, 92093, USA. mburkart@ucsd.edu.
  • Tsai SC; Department of Molecular Biology and Biochemistry, Chemistry, and Pharmaceutical Sciences, University of California, Irvine, Irvine, CA, 92697, USA. sctsai@uci.edu.
Angew Chem Int Ed Engl ; 55(42): 13005-13009, 2016 10 10.
Article em En | MEDLINE | ID: mdl-27653519
ABSTRACT
In fungal non-reducing polyketide synthases (NR-PKS) the acyl-carrier protein (ACP) carries the growing polyketide intermediate through iterative rounds of elongation, cyclization and product release. This process occurs through a controlled, yet enigmatic coordination of the ACP with its partner enzymes. The transient nature of ACP interactions with these catalytic domains imposes a major obstacle for investigation of the influence of protein-protein interactions on polyketide product outcome. To further our understanding about how the ACP interacts with the product template (PT) domain that catalyzes polyketide cyclization, we developed the first mechanism-based crosslinkers for NR-PKSs. Through in vitro assays, in silico docking and bioinformatics, ACP residues involved in ACP-PT recognition were identified. We used this information to improve ACP compatibility with non-cognate PT domains, which resulted in the first gain-of-function ACP with improved interactions with its partner enzymes. This advance will aid in future combinatorial biosynthesis of new polyketides.
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Texto completo: 1 Base de dados: MEDLINE Assunto principal: Proteína de Transporte de Acila / Policetídeos Idioma: En Ano de publicação: 2016 Tipo de documento: Article
Texto completo
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PubMed Links
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Texto completo: 1 Base de dados: MEDLINE Assunto principal: Proteína de Transporte de Acila / Policetídeos Idioma: En Ano de publicação: 2016 Tipo de documento: Article