Crystal structure of glutamate dehydrogenase 3 from Candida albicans

Biochem Biophys Res Commun. 2021 Sep 17:570:15-20. doi: 10.1016/j.bbrc.2021.07.014. Epub 2021 Jul 13.

Abstract

Glutamate dehydrogenase 3 from Candida albicans (CaGdh3) catalyzes the reversible oxidative deamination of l-glutamate, playing an important role in the yeast-to-hyphal transition of C. albicans. Here we report the crystal structures of CaGdh3 and its complex with α-ketoglutarate and NADPH. CaGdh3 exists as a hexamer, with each subunit containing two domains. The substrate and coenzyme bind in the cleft between the two domains and their binding induces a conformational change in CaGdh3. Our results will help to understand the catalytic mechanism of CaGdh3 and will provide a structural basis for the design of antifungal drugs targeting the CaGdh3 pathway.

Keywords: Candida albicans; Conformational change; Crystal structure; Glutamate dehydrogenase; Yeast-to-hyphal transition.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Candida albicans / enzymology*
  • Catalytic Domain
  • Coenzymes / metabolism
  • Crystallography, X-Ray
  • Fungal Proteins / chemistry*
  • Glutamate Dehydrogenase / chemistry*
  • Models, Molecular
  • NADP / chemistry
  • NADP / metabolism
  • Protein Conformation
  • Protein Multimerization
  • Solutions
  • Substrate Specificity

Substances

  • Coenzymes
  • Fungal Proteins
  • Solutions
  • NADP
  • Glutamate Dehydrogenase