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Hexachlorobenzene monooxygenase (HcbA1) from Nocardioides sp. strain PD653 complexed with FMN
Structural highlights
FunctionPublication Abstract from PubMedHexachlorobenzene (HCB), as one of the persistent organic pollutants (POPs) and a possible human carcinogen, is especially resistant to biodegradation. In this study, HcbA1A3, a distinct flavin-N5-peroxide utilizing enzyme and the sole known naturally occurring aerobic HCB dechlorinase, was biochemically characterized. Its apparent preference for HCB in binding affinity determined that HcbA1 could only oxidize HCB rather than less chlorinated benzenes such as pentachlorobenzene and tetrachlorobenzenes. In addition, the crystal structure of HcbA1 and its complex with FMN were resolved, revealing HcbA1 as a new member of the bacterial luciferase-like family. Compared with its close homologues, a much smaller substrate-binding pocket of HcbA1 suggests a requirement of limited space for catalysis. In the active center, Tyr362 and Asp315 are necessary in maintaining the normal conformation of HcbA1, while Arg311, Arg314, Phe10, Val59, and Met12 are pivotal for the substrate-affinity. They are supposed to place HCB at a productive orientation through multiple interactions. His17, with its close contact with the site of oxidation of HCB, probably fixes target chlorine atom and stabilizes reaction intermediates. The enzymatic characteristics and crystal structures reported here provide new insights into the substrate specificity and catalytic mechanism of HcbA1, which paves the way for its rational engineering and application in the bioremediation of HCB polluted environments.IMPORTANCE As an endocrine disrupter and possible carcinogen to human beings, hexachlorobenzene (HCB) is especially resistant to biodegradation, largely due to its difficulty in dechlorination. The lack of knowledge for HCB dechlorinases limits their application in bioremediation. Recently, an HCB monooxygenase HcbA1A3 was reported, which is the only known naturally occurring aerobic HCB dechlorinase so far. Here we report its biochemical and structural characterizations, which provide new insights into its substrate selectivity and catalytic mechanism. This research also increases our understanding of HCB dechlorinases and flavin-N5-peroxide utilizing enzymes. Structural and biochemical insights into the substrate selectivity and catalysis of hexachlorobenzene monooxygenase.,Guo Y, Li DF, Ji H, Zheng J, Zhou NY Appl Environ Microbiol. 2020 Oct 23. pii: AEM.01965-20. doi:, 10.1128/AEM.01965-20. PMID:33097503[1] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. References
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