title: Cofactor-induced reversible folding of Flavodoxin-4 from Lactobacillus acidophilus.
abstract: Flavodoxins in combination with the flavin mononucleotide (FMN) cofactor play important roles for electron transport in prokaryotes. Here, novel insights into the FMN-binding mechanism to flavodoxins-4 were obtained from the NMR structures of the apo-protein from Lactobacillus acidophilus (YP_193882.1) and comparison of its complex with FMN. Extensive reversible conformational changes were observed upon FMN binding and release. The NMR structure of the FMN complex is in agreement with the crystal structure (PDB ID: 3EDO) and exhibits the characteristic flavodoxin fold, with a central five-stranded parallel β-sheet and five α-helices forming an α/β-sandwich architecture. The structure differs from other flavoproteins in that helix α2 is oriented perpendicular to the β-sheet and covers the FMN-binding site. This helix reversibly unfolds upon removal of the FMN ligand, which represents a unique structural rearrangement among flavodoxins.
authors.affiliation: Joint Center for Structural Genomics, La Jolla, California, 92037.|Department of Integrative Structural and Computational Biology, the Scripps Research Institute, La Jolla, California, 92037.
authors.forename: Samit Kumar
authors.initials: SK
authors.lastname: Dutta
authors.affiliation: Joint Center for Structural Genomics, La Jolla, California, 92037.|Department of Integrative Structural and Computational Biology, the Scripps Research Institute, La Jolla, California, 92037.
authors.forename: Pedro
authors.initials: P
authors.lastname: Serrano
authors.affiliation: Joint Center for Structural Genomics, La Jolla, California, 92037.|Department of Integrative Structural and Computational Biology, the Scripps Research Institute, La Jolla, California, 92037.
authors.forename: Michael
authors.initials: M
authors.lastname: Geralt
authors.affiliation: Joint Center for Structural Genomics, La Jolla, California, 92037.|SLAC National Accelerator Laboratory, Stanford Synchrotron Radiation Lightsource, California, 94025.
authors.forename: Herbert L
authors.initials: HL
authors.lastname: Axelrod
authors.affiliation: Joint Center for Structural Genomics, La Jolla, California, 92037.|SLAC National Accelerator Laboratory, Stanford Synchrotron Radiation Lightsource, California, 94025.
authors.forename: Qingping
authors.initials: Q
authors.lastname: Xu
authors.affiliation: Joint Center for Structural Genomics, La Jolla, California, 92037.|Department of Integrative Structural and Computational Biology, the Scripps Research Institute, La Jolla, California, 92037.|Protein Sciences Department, Genomics Institute of the Novartis Research Foundation, San Diego, California, 92121.
authors.forename: Scott A
authors.initials: SA
authors.lastname: Lesley
authors.affiliation: Joint Center for Structural Genomics, La Jolla, California, 92037.|Program on Bioinformatics and Systems Biology, Sanford-Burnham Medical Research Institute, La Jolla, California, 92037.|Center for Research in Biological Systems, University of California, San Diego, La Jolla, California, 92093.
authors.forename: Adam
authors.initials: A
authors.lastname: Godzik
authors.affiliation: Joint Center for Structural Genomics, La Jolla, California, 92037.|SLAC National Accelerator Laboratory, Stanford Synchrotron Radiation Lightsource, California, 94025.
authors.forename: Ashley M
authors.initials: AM
authors.lastname: Deacon
authors.affiliation: Joint Center for Structural Genomics, La Jolla, California, 92037.|Department of Integrative Structural and Computational Biology, the Scripps Research Institute, La Jolla, California, 92037.
authors.forename: Marc-André
authors.initials: MA
authors.lastname: Elsliger
authors.affiliation: Joint Center for Structural Genomics, La Jolla, California, 92037.|Department of Integrative Structural and Computational Biology, the Scripps Research Institute, La Jolla, California, 92037.|Skaggs Institute for Chemical Biology, the Scripps Research Institute, La Jolla, California, 92037.
authors.forename: Ian A
authors.initials: IA
authors.lastname: Wilson
authors.affiliation: Joint Center for Structural Genomics, La Jolla, California, 92037.|Department of Integrative Structural and Computational Biology, the Scripps Research Institute, La Jolla, California, 92037.|Skaggs Institute for Chemical Biology, the Scripps Research Institute, La Jolla, California, 92037.
authors.forename: Kurt
authors.initials: K
authors.lastname: Wüthrich
mesh_terms: D000595:Amino Acid Sequence; D018360:Crystallography, X-Ray; D004579:Electron Transport; D005486:Flavin Mononucleotide / Q000737:chemistry*; D005418:Flavodoxin / Q000737:chemistry* / Q000378:metabolism; D007779:Lactobacillus acidophilus / Q000737:chemistry* / Q000201:enzymology; D009682:Magnetic Resonance Spectroscopy; D011485:Protein Binding; D017510:Protein Folding
chemical_list: D005418:Flavodoxin; D005486:Flavin Mononucleotide
keywords: cofactor binding; flavin mononucleotide; protein folding; protein-ligand interaction