title: Structural analysis of a phosphonate hydroxylase with an access tunnel at the back of the active site.
abstract: FrbJ is a member of the Fe(2+)/α-ketoglutarate-dependent dioxygenase family which hydroxylates the natural product FR-900098 of Streptomyces rubellomurinus, yielding the phosphonate antibiotic FR-33289. Here, the crystal structure of FrbJ, which shows structural homology to taurine dioxygenase (TauD), a key member of the same family, is reported. Unlike other members of the family, FrbJ has an unusual lid structure which consists of two β-strands with a long loop between them. To investigate the role of this lid motif, a molecular-dynamics simulation was performed with the FrbJ structure. The molecular-dynamics simulation analysis implies that the lid-loop region is highly flexible, which is consistent with the fact that FrbJ has a relatively broad spectrum of substrates with different lengths. Interestingly, an access tunnel is found at the back of the active site which connects the putative binding site of α-ketoglutarate to the solvent outside.
authors.affiliation: Department of Biotechnology, College of Life Science and Technology, Huazhong University of Science and Technology, Wuhan, People's Republic of China.
authors.forename: Changqing
authors.initials: C
authors.lastname: Li
authors.affiliation: Department of Biotechnology, College of Life Science and Technology, Huazhong University of Science and Technology, Wuhan, People's Republic of China.
authors.forename: Muhammad
authors.initials: M
authors.lastname: Junaid
authors.affiliation: Department of Biotechnology, College of Life Science and Technology, Huazhong University of Science and Technology, Wuhan, People's Republic of China.
authors.forename: Eman Abdullah
authors.initials: EA
authors.lastname: Almuqri
authors.affiliation: Department of Biotechnology, College of Life Science and Technology, Huazhong University of Science and Technology, Wuhan, People's Republic of China.
authors.forename: Shiguang
authors.initials: S
authors.lastname: Hao
authors.affiliation: Department of Biotechnology, College of Life Science and Technology, Huazhong University of Science and Technology, Wuhan, People's Republic of China.
authors.forename: Houjin
authors.initials: H
authors.lastname: Zhang
mesh_terms: D020134:Catalytic Domain; D003460:Crystallization; D006900:Hydroxylation; D006899:Mixed Function Oxygenases / Q000737:chemistry*; D056004:Molecular Dynamics Simulation; D013302:Streptomyces / Q000201:enzymology
chemical_list: D006899:Mixed Function Oxygenases
keywords: FrbJ; access tunnel; crystal structure; hydroxylase