6OHJ

Crystal Structure of the Debrominase Bmp8 C82A in Complex with 2,3,4-tribromopyrrole

Summary for 6OHJ

• Entry DOI: 10.2210/pdb6ohj/pdb
• Descriptor: Debrominase Bmp8, SULFATE ION, 2,3,4-tribromo-1H-pyrrole, ... (4 entities in total)
• Functional Keywords: debrominase, biosynthetic protein
• Biological source: Marinomonas mediterranea MMB-1
• Total number of polymer chains: 2
• Total formula weight: 43514.63

Authors

Chekan, J.R.,Moore, B.S. (deposition date: 2019-04-05, release date: 2019-05-29, Last modification date: 2024-03-06)

Primary citation

Chekan, J.R.,Lee, G.Y.,El Gamal, A.,Purdy, T.N.,Houk, K.N.,Moore, B.S.
Bacterial Tetrabromopyrrole Debrominase Shares a Reductive Dehalogenation Strategy with Human Thyroid Deiodinase.
Biochemistry, 58:5329-5338, 2019

PubMed Abstract: Enzymatic dehalogenation is an important and well-studied biological process in both the detoxification and catabolism of small molecules, many of which are anthropogenic in origin. However, dedicated dehalogenation reactions that replace a halogen atom with a hydrogen are rare in the biosynthesis of natural products. In fact, the debrominase Bmp8 is the only known example. It catalyzes the reductive debromination of the coral settlement cue and the potential human toxin 2,3,4,5-tetrabromopyrrole as part of the biosynthesis of the antibiotic pentabromopseudilin. Using a combination of protein crystallography, mutagenesis, and computational modeling, we propose a catalytic mechanism for Bmp8 that is reminiscent of that catalyzed by human deiodinases in the maintenance of thyroid hormones. The identification of the key catalytic residues enabled us to recognize divergent functional homologues of Bmp8. Characterization of one of these homologues demonstrated its debromination activity even though it is found in a completely distinct genomic context. This observation suggests that additional enzymes outside those associated with the tetrabromopyrrole biosynthetic pathway may be able to alter the lifetime of this compound in the environment.

PubMed: 31117392
DOI: 10.1021/acs.biochem.9b00318

Experimental method

X-RAY DIFFRACTION (3.19 Å)