Structural analysis of a phosphonate hydroxylase with an access tunnel at the back of the active site

• Published in: Acta crystallographica. Section F, Structural biology communications Structural biology communications, 2016-05, Vol.72 (5), p.362-368
• Main Authors: Li, Changqing, Junaid, Muhammad, Almuqri, Eman Abdullah, Hao, Shiguang, Zhang, Houjin
• Format: Article
• Language: English
• Subjects: access tunnel; Binding sites; Biology; Catalytic Domain; Crystal structure; Crystallization; FrbJ; hydroxylase; Hydroxylation; Mixed Function Oxygenases - chemistry; Molecular dynamics; Molecular Dynamics Simulation; Phosphonates; Research Communications; Simulation; Solvents; Streptomyces - enzymology; Tunnels (transportation)
• ISSN: 2053-230X; 2053-230X
• DOI: 10.1107/S2053230X16004933

FrbJ is a member of the Fe2+/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. The crystal structure of the dioxygenase FrbJ is reported. An access tunnel was found at the back of the active site, which connects the putative binding site for α‐ketoglutarate to the solvent.