title: Structures of apo and GTP-bound molybdenum cofactor biosynthesis protein MoaC from Thermus thermophilus HB8.
abstract: The first step in the molybdenum cofactor (Moco) biosynthesis pathway involves the conversion of guanosine triphosphate (GTP) to precursor Z by two proteins (MoaA and MoaC). MoaA belongs to the S-adenosylmethionine-dependent radical enzyme superfamily and is believed to generate protein and/or substrate radicals by reductive cleavage of S-adenosylmethionine using an Fe-S cluster. MoaC has been suggested to catalyze the release of pyrophosphate and the formation of the cyclic phosphate of precursor Z. However, structural evidence showing the binding of a substrate-like molecule to MoaC is not available. Here, apo and GTP-bound crystal structures of MoaC from Thermus thermophilus HB8 are reported. Furthermore, isothermal titration calorimetry experiments have been carried out in order to obtain thermodynamic parameters for the protein-ligand interactions. In addition, molecular-dynamics (MD) simulations have been carried out on the protein-ligand complex of known structure and on models of relevant complexes for which X-ray structures are not available. The biophysical, structural and MD results reveal the residues that are involved in substrate binding and help in speculating upon a possible mechanism.
authors.affiliation: Bioinformatics Centre (Centre of Excellence in Structural Biology and Bio-computing), Indian Institute of Science, Bangalore, India.
authors.forename: Shankar Prasad
authors.initials: SP
authors.lastname: Kanaujia
authors.forename: Jeyaraman
authors.initials: J
authors.lastname: Jeyakanthan
authors.forename: Noriko
authors.initials: N
authors.lastname: Nakagawa
authors.forename: Sathyaramya
authors.initials: S
authors.lastname: Balasubramaniam
authors.forename: Akeo
authors.initials: A
authors.lastname: Shinkai
authors.forename: Seiki
authors.initials: S
authors.lastname: Kuramitsu
authors.forename: Shigeyuki
authors.initials: S
authors.lastname: Yokoyama
authors.forename: Kanagaraj
authors.initials: K
authors.lastname: Sekar
mesh_terms: D000595:Amino Acid Sequence; D001059:Apoproteins / Q000737:chemistry* / Q000378:metabolism; D001426:Bacterial Proteins / Q000737:chemistry* / Q000378:metabolism; D001665:Binding Sites; D003067:Coenzymes / Q000096:biosynthesis; D017124:Conserved Sequence; D018360:Crystallography, X-Ray; D006160:Guanosine Triphosphate / Q000737:chemistry* / Q000378:metabolism; D008667:Metalloproteins / Q000096:biosynthesis; D008958:Models, Molecular; D008969:Molecular Sequence Data; D000090006:Molybdenum Cofactors; D011485:Protein Binding; D020836:Protein Structure, Quaternary; D017434:Protein Structure, Tertiary; D011621:Pteridines; D016415:Sequence Alignment; D016963:Thermus thermophilus / Q000737:chemistry* / Q000378:metabolism
chemical_list: D001059:Apoproteins; D001426:Bacterial Proteins; D003067:Coenzymes; D006160:Guanosine Triphosphate; D008667:Metalloproteins; D000090006:Molybdenum Cofactors; D011621:Pteridines; C022261:molybdopterin