Structural and functional comparison of fumarylacetoacetate domain containing protein 1 in human and mouse

Biosci Rep. 2020 Mar 27;40(3):BSR20194431. doi: 10.1042/BSR20194431.


FAH domain containing protein 1 (FAHD1) is a mammalian mitochondrial protein, displaying bifunctionality as acylpyruvate hydrolase (ApH) and oxaloacetate decarboxylase (ODx) activity. We report the crystal structure of mouse FAHD1 and structural mapping of the active site of mouse FAHD1. Despite high structural similarity with human FAHD1, a rabbit monoclonal antibody (RabMab) could be produced that is able to recognize mouse FAHD1, but not the human form, whereas a polyclonal antibody recognized both proteins. Epitope mapping in combination with our deposited crystal structures revealed that the epitope overlaps with a reported SIRT3 deacetylation site in mouse FAHD1.

Keywords: FAHD1; SIRT3; crystallography.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Acetoacetates / metabolism
  • Animals
  • Carboxy-Lyases / metabolism
  • Catalytic Domain
  • Crystallography, X-Ray
  • Epitope Mapping / methods
  • Humans
  • Hydrolases / chemistry
  • Hydrolases / genetics*
  • Hydrolases / metabolism
  • Mice
  • Mitochondria / metabolism
  • Mitochondrial Proteins / metabolism
  • Structure-Activity Relationship


  • Acetoacetates
  • Mitochondrial Proteins
  • fumarylacetoacetate
  • FAHD1 protein, human
  • Fahd2a protein, mouse
  • Hydrolases
  • Carboxy-Lyases
  • oxaloacetate decarboxylase