Structure of the methanofuran/methanopterin-biosynthetic enzyme MJ1099 from Methanocaldococcus jannaschii.
Prior studies have indicated that MJ1099 from Methanocaldococcus jannaschii has roles in the biosynthesis of tetrahydromethanopterin and methanofuran, two key cofactors of one-carbon (C1) metabolism in diverse organisms including the methanogenic archaea. Here, the structure of MJ1099 has been solved to 1.7 Å resolution using anomalous scattering methods. The results indicate that MJ1099 is a member of the TIM-barrel superfamily and that it is a homohexamer. Bioinformatic analyses identified a potential active site that is highly conserved among MJ1099 homologs and the key amino acids involved were identified. The results presented here should guide further studies of MJ1099 including mechanistic studies and possibly the development of inhibitors that target the methanogenic archaea in the digestive tracts of humans and that are a source of the greenhouse gas methane.
Roy J. Carver Department of Biochemistry, Biophysics and Molecular Biology, Iowa State University, Ames, IA 50011, USA.
Thomas A
TA
Bobik
Department of Chemistry and Biochemistry, California State University, Fullerton, CA 92834, USA.
Erick J
EJ
Morales
Department of Energy Institute for Genomics and Proteomics, University of California Los Angeles, Los Angeles, CA 90095, USA.
Annie
A
Shin
Department of Energy Institute for Genomics and Proteomics, University of California Los Angeles, Los Angeles, CA 90095, USA.
Duilio
D
Cascio
Department of Energy Institute for Genomics and Proteomics, University of California Los Angeles, Los Angeles, CA 90095, USA.
Michael R
MR
Sawaya
Department of Energy Institute for Genomics and Proteomics, University of California Los Angeles, Los Angeles, CA 90095, USA.
Mark
M
Arbing
Department of Energy Institute for Genomics and Proteomics, University of California Los Angeles, Los Angeles, CA 90095, USA.
Todd O
TO
Yeates
Department of Chemistry and Biochemistry, California State University, Fullerton, CA 92834, USA.
Madeline E
ME
Rasche
D001426:Bacterial Proteins / Q000737:chemistry* / Q000378:metabolism; D001665:Binding Sites / Q000502:physiology; D003461:Crystallography; D005663:Furans / Q000737:chemistry* / Q000378:metabolism; D063747:Methanocaldococcus / Q000201:enzymology*; D017433:Protein Structure, Secondary; D017434:Protein Structure, Tertiary; D011622:Pterins / Q000737:chemistry* / Q000378:metabolism; D011994:Recombinant Proteins / Q000737:chemistry / Q000378:metabolism
D001426:Bacterial Proteins; D005663:Furans; D011622:Pterins; D011994:Recombinant Proteins; C036686:methanopterin; C044289:carbon dioxide reduction factor
MJ1099; Methanocaldococcus jannaschii; methanofuran; methanopterin