5LV9

Crystal structure of thermophilic tryptophan halogenase (Th-Hal) enzyme from Streptomycin violaceusniger.

Summary for 5LV9

• Entry DOI: 10.2210/pdb5lv9/pdb
• Descriptor: thermophilic tryptophan halogenase (2 entities in total)
• Functional Keywords: thermophilic, flavin reductase, enzyme, hydrolase
• Biological source: Streptomyces violaceusniger
• Total number of polymer chains: 2
• Total formula weight: 115938.67

Authors

Dunstan, M.S.,Menon, B. (deposition date: 2016-09-13, release date: 2016-10-19, Last modification date: 2024-05-08)

Primary citation

Menon, B.R.,Latham, J.,Dunstan, M.S.,Brandenburger, E.,Klemstein, U.,Leys, D.,Karthikeyan, C.,Greaney, M.F.,Shepherd, S.A.,Micklefield, J.
Structure and biocatalytic scope of thermophilic flavin-dependent halogenase and flavin reductase enzymes.
Org.Biomol.Chem., 14:9354-9361, 2016

PubMed Abstract: Flavin-dependent halogenase (Fl-Hal) enzymes have been shown to halogenate a range of synthetic as well as natural aromatic compounds. The exquisite regioselectively of Fl-Hal enzymes can provide halogenated building blocks which are inaccessible using standard halogenation chemistries. Consequently, Fl-Hal are potentially useful biocatalysts for the chemoenzymatic synthesis of pharmaceuticals and other valuable products, which are derived from haloaromatic precursors. However, the application of Fl-Hal enzymes, in vitro, has been hampered by their poor catalytic activity and lack of stability. To overcome these issues, we identified a thermophilic tryptophan halogenase (Th-Hal), which has significantly improved catalytic activity and stability, compared with other Fl-Hal characterised to date. When used in combination with a thermostable flavin reductase, Th-Hal can efficiently halogenate a number of aromatic substrates. X-ray crystal structures of Th-Hal, and the reductase partner (Th-Fre), provide insights into the factors that contribute to enzyme stability, which could guide the discovery and engineering of more robust and productive halogenase biocatalysts.

PubMed: 27714222
DOI: 10.1039/c6ob01861k

Experimental method

X-RAY DIFFRACTION (2.33 Å)