HutZ from Aliivibrio fischeri Inhibits HutW-Mediated Anaerobilin Formation by Sequestering Heme.

IF 2.9 3区 生物学 Q3 BIOCHEMISTRY & MOLECULAR BIOLOGY
Biochemistry Biochemistry Pub Date : 2024-12-17 Epub Date: 2024-12-06 DOI:10.1021/acs.biochem.4c00624
Alexandra K McGregor, Kirsten R Wolthers
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引用次数: 0

Abstract

Anaerobilin synthase catalyzes the decyclization of the heme protoporphyrin ring, an O2-independent reaction that liberates iron and produces the linear tetrapyrrole, anaerobilin. The marine bacterium Aliivibrio fischeri, the enteric pathogen Escherichia coli O157:H7, and the opportunistic oral pathogen Fusobacterium nucleatum encode anaerobilin synthase as part of their heme uptake/utilization operons, designated chu (E. coli O157:H7), hmu (F. nucleatum), and hut (A. fischeri). F. nucleatum and E. coli O157:H7 contain accessory proteins (ChuS, ChuY, and HmuF) encoded in their respective operons that mitigate against the cytotoxicity of labile heme and anaerobilin by functioning in heme trafficking and anaerobilin reduction. However, the hut operon of A. fischeri and other members of the Vibrionaceae family including the enteric pathogen Vibrio cholerae do not contain homologues to these accessory proteins, raising questions as to how members of this family mitigate against anaerobilin and heme toxicity. Herein, we show that HutW (anaerobilin synthase) from A. fischeri produces anaerobilin, but that HutX and HutZ, encoded downstream of HutW, do not catalyze anaerobilin reduction in the presence of excess NAD(P)H, FAD, and FMN. However, we show that HutZ prevents labile heme and anaerobilin cytotoxicity by binding tightly to heme, sequestering it from HutW, and preventing anaerobilin formation. Thus, A. fischeri is seemingly unable to extract iron from heme using the hutWXZ gene products. Our results further suggest that the structurally distinct chu, hmu, and hut operons have functionally converged to protect the cell from anaerobilin accumulation and heme cytotoxicity.

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来源期刊
Biochemistry Biochemistry
Biochemistry Biochemistry 生物-生化与分子生物学
CiteScore
5.50
自引率
3.40%
发文量
336
审稿时长
1-2 weeks
期刊介绍: Biochemistry provides an international forum for publishing exceptional, rigorous, high-impact research across all of biological chemistry. This broad scope includes studies on the chemical, physical, mechanistic, and/or structural basis of biological or cell function, and encompasses the fields of chemical biology, synthetic biology, disease biology, cell biology, nucleic acid biology, neuroscience, structural biology, and biophysics. In addition to traditional Research Articles, Biochemistry also publishes Communications, Viewpoints, and Perspectives, as well as From the Bench articles that report new methods of particular interest to the biological chemistry community.
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