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

Acta Crystallogr F Struct Biol Commun. 2016 May;72(Pt 5):362-8. doi: 10.1107/S2053230X16004933. Epub 2016 Apr 22.

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.

Keywords: FrbJ; access tunnel; crystal structure; hydroxylase.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Catalytic Domain
  • Crystallization
  • Hydroxylation
  • Mixed Function Oxygenases / chemistry*
  • Molecular Dynamics Simulation
  • Streptomyces / enzymology

Substances

  • Mixed Function Oxygenases