Crystal structure of the apurinic/apyrimidinic endonuclease IV from Mycobacterium tuberculosis

Zhang, Wei; Xu, Yueyang; Yan, Mengrong; Li, Shanshan; Wang, Huiying; Yang, Haitao; Zhou, Weihong; Rao, Zihe

doi:10.1016/j.bbrc.2018.02.181

Cited by 7 publications

(3 citation statements)

References 23 publications

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“…As a member of the AP endonuclease 2 superfamily, CbiR likely contains a (b/a) 8 TIM barrel domain (83)(84)(85)(86)(87)(88)(89)(90)(91)(92)(93)(94)(95)(96)(97), unlike the structures predicted for the CbiZ and CobS protein families (109). Thus, not only does CbiR catalyze a unique reaction, but it is also distinct from the other cobamide remodeling enzymes in sequence and likely in S1).…”

Section: Discussionmentioning

confidence: 99%

Identification of a Novel Cobamide Remodeling Enzyme in the Beneficial Human Gut Bacterium Akkermansia muciniphila

Mok

Sokolovskaya

Nicolas

et al. 2020

mBio

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The beneficial human gut bacterium Akkermansia muciniphila provides metabolites to other members of the gut microbiota by breaking down host mucin, but most of its other metabolic functions have not been investigated. A. muciniphila strain MucT is known to use cobamides, the vitamin B12 family of cofactors with structural diversity in the lower ligand. However, A. muciniphila MucT is unable to synthesize cobamides de novo, and the specific forms that can be used by A. muciniphila have not been examined. We found that the levels of growth of A. muciniphila MucT were nearly identical with each of seven cobamides tested, in contrast to nearly all bacteria that had been studied previously. Unexpectedly, this promiscuity is due to cobamide remodeling—the removal and replacement of the lower ligand—despite the absence of the canonical remodeling enzyme CbiZ in A. muciniphila. We identified a novel enzyme, CbiR, that is capable of initiating the remodeling process by hydrolyzing the phosphoribosyl bond in the nucleotide loop of cobamides. CbiR does not share similarity with other cobamide remodeling enzymes or B12-binding domains and is instead a member of the apurinic/apyrimidinic (AP) endonuclease 2 enzyme superfamily. We speculate that CbiR enables bacteria to repurpose cobamides that they cannot otherwise use in order to grow under cobamide-requiring conditions; this function was confirmed by heterologous expression of cbiR in Escherichia coli. Homologs of CbiR are found in over 200 microbial taxa across 22 phyla, suggesting that many bacteria may use CbiR to gain access to the diverse cobamides present in their environment. IMPORTANCE Cobamides, comprising the vitamin B12 family of cobalt-containing cofactors, are required for metabolism in all domains of life, including most bacteria. Cobamides have structural variability in the lower ligand, and selectivity for particular cobamides has been observed in most organisms studied to date. Here, we discovered that the beneficial human gut bacterium Akkermansia muciniphila can use a diverse range of cobamides due to its ability to change the cobamide structure via a process termed cobamide remodeling. We identify and characterize the novel enzyme CbiR that is necessary for initiating the cobamide remodeling process. The discovery of this enzyme has implications for understanding the ecological role of A. muciniphila in the gut and the functions of other bacteria that produce this enzyme.

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Section: Discussionmentioning

confidence: 99%

Identification of a Novel Cobamide Remodeling Enzyme in the Beneficial Human Gut Bacterium Akkermansia muciniphila

Mok

Sokolovskaya

Nicolas

et al. 2020

mBio

View full text Add to dashboard Cite

show abstract

“…As a member of the AP endonuclease 2 superfamily, CbiR likely contains a (β/α)8 TIM barrel domain (63)(64)(65)(66)(67)(68)(69)(70)(71)(72)(73)(74)(75)(76)(77), unlike the structures predicted for the CbiZ and CobS protein families (80). Thus, not only does CbiR catalyze a unique reaction, but it is also distinct from the other cobamide remodeling enzymes in sequence and likely in structure.…”

Section: Discussionmentioning

confidence: 99%

“…6A). Some of the biochemically characterized enzymes in the superfamily require metal cofactors for activity, and between one and three metal ions are found in nearly all X-ray crystal structures of enzymes from the superfamily (63)(64)(65)(66)(67)(68)(69)(70)(71)(72)(73)(74)(75)(76)(77). A metal cofactor may also be required for CbiR function; in addition to the inhibition by the metal chelator EDTA (Fig.…”

Section: Cbir Is a Member Of The Ap Endonuclease 2 Superfamily And Ismentioning

confidence: 99%

Identification of a novel cobamide remodeling enzyme in the beneficial human gut bacteriumAkkermansia muciniphila

Mok

Sokolovskaya

Nicolas

et al. 2020

Preprint

View full text Add to dashboard Cite

The beneficial human gut bacterium Akkermansia muciniphila provides metabolites to other members of the gut microbiota by breaking down host mucin, but most of its other metabolic functions have not been investigated. A. muciniphila is known to use cobamides, the vitamin B12 family of cofactors with structural diversity in the lower ligand, though the specific cobamides it can use have not been examined. We found that growth of A. muciniphila strain MucT was nearly identical with each of seven cobamides tested, in contrast to nearly all bacteria that have been studied. Unexpectedly, this promiscuity is due to cobamide remodeling – the removal and replacement of the lower ligand – despite the absence of the canonical remodeling enzyme CbiZ in A. muciniphila. We identified a novel enzyme, CbiR, that is capable of initiating the remodeling process by hydrolyzing the phosphoribosyl bond in the nucleotide loop of cobamides. CbiR does not share homology with other cobamide remodeling enzymes or B12-binding domains, and instead is a member of the AP endonuclease 2 enzyme superfamily. We speculate that CbiR enables bacteria to repurpose cobamides they otherwise cannot use in order to grow under a cobamide-requiring condition; this function was confirmed by heterologous expression of cbiR in E. coli. Homologs of CbiR are found in over 200 microbial taxa across 22 phyla, suggesting that many bacteria may use CbiR to gain access to the diverse cobamides present in their environment.ImportanceCobamides, the vitamin B12 family of cobalt-containing cofactors, are required for metabolism in all domains of life, including most bacteria. Cobamides have structural variability in the lower ligand, and selectivity for particular cobamides has been observed in most organisms studied to date. Here, we discover that the beneficial human gut bacterium Akkermansia muciniphila can use a diverse range of cobamides due to its ability to change the cobamide structure via “cobamide remodeling”. We identify and characterize the novel enzyme CbiR that is necessary for initiating the cobamide remodeling process. The discovery of this enzyme has implications not only for understanding the ecological role of A. muciniphila in the gut, but for other bacteria that carry this enzyme as well.

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Purification, crystallization and preliminary crystallographic analysis of Chlamydophila pneumoniae AP endonuclease IV

Zhang,

Ren,

Wang

et al. 2024

Protein Expression and Purification

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Crystal structure of the apurinic/apyrimidinic endonuclease IV from Mycobacterium tuberculosis

Cited by 7 publications

References 23 publications

Identification of a Novel Cobamide Remodeling Enzyme in the Beneficial Human Gut Bacterium Akkermansia muciniphila

Identification of a Novel Cobamide Remodeling Enzyme in the Beneficial Human Gut Bacterium Akkermansia muciniphila

Identification of a novel cobamide remodeling enzyme in the beneficial human gut bacteriumAkkermansia muciniphila

Purification, crystallization and preliminary crystallographic analysis of Chlamydophila pneumoniae AP endonuclease IV

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