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Crystal Structure and Bioinformatics Inferred Function of Protein A2617 from Methylibium petroleiphilum
Author(s) -
Saleh Ali,
Collazo Michael J.,
Sawaya Michael,
Cascio Duilio,
Rasche Madeline
Publication year - 2016
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.30.1_supplement.601.9
Subject(s) - chemistry , archaea , oxidoreductase , homology modeling , monomer , docking (animal) , hydrolase , stereochemistry , crystallography , protein structure , crystal structure , ligand (biochemistry) , structural genomics , biochemistry , enzyme , gene , medicine , receptor , nursing , organic chemistry , polymer
The attempt to elucidate the biological function of enzymes involved in the biosynthesis of tetrahydromethanopterin for the use in one‐carbon metabolism by archaea and select bacteria has resulted in the crystal structure of the hypothetical protein A2617 from Methylibium petroleiphilum . The structure was initially solved at 2.0 Å resolution using a selenomethionine multi‐wavelength anomalous diffraction experiment, and further refined at 1.8 Å resolution using a native dataset. The Rfactor of the current model is 0.19 and the Rfree is 0.22. The crystal structure of A2617 is a homodimer with each monomer consisting of four α‐helices connected to a barrel fold of six anti‐parallel β‐sheets with an α‐helix by a pair of anti‐parallel β‐sheets. The monomers interface to form the homodimer at the region containing four α‐helices with the barrel folds flanking both ends of the structure. A deep cleft is present at the interface of the two monomers. The overall structure of A2617 resembles that of uncharacterized archaeal homologs; however, the structure is distinct due to the lack of bound FMN in the binding pocket that is found in the archaeal homolog crystal structures. Ligand docking studies using intermediates in the tetrahydromethanopterin biosynthetic pathway indicated that A2617 has the greatest binding affinity for 6‐hydroxymethyl‐7,8‐dihydropterin‐ribofuranosylaminobenzene‐5‐phosphate. This metabolite is the substrate for the third step of tetrahydromethanopterin side chain biosynthesis, which is an oxidoreductase reaction. The homology of A2617 with FMN‐containing archaeal proteins and the findings of the ligand binding studies provide support for the role of A2617 in catalyzing a reductive reaction in the biosynthesis of the tetrahydromethanopterin side chain. Support or Funding Information This research was supported by National Science Foundation grant number CHE‐1508801 and by a grant from the California State University Program for Education and Research in Biotechnology (CSUPERB).