دورية أكاديمية
Copper binding by a unique family of metalloproteins is dependent on kynurenine formation.
| العنوان: | Copper binding by a unique family of metalloproteins is dependent on kynurenine formation. |
|---|---|
| المؤلفون: | Manesis AC; Department of Molecular Biosciences, Northwestern University, Evanston, IL 60208.; Department of Chemistry, Northwestern University, Evanston, IL 60208., Jodts RJ; Department of Molecular Biosciences, Northwestern University, Evanston, IL 60208.; Department of Chemistry, Northwestern University, Evanston, IL 60208., Hoffman BM; Department of Molecular Biosciences, Northwestern University, Evanston, IL 60208.; Department of Chemistry, Northwestern University, Evanston, IL 60208., Rosenzweig AC; Department of Molecular Biosciences, Northwestern University, Evanston, IL 60208; amyr@northwestern.edu.; Department of Chemistry, Northwestern University, Evanston, IL 60208. |
| المصدر: | Proceedings of the National Academy of Sciences of the United States of America [Proc Natl Acad Sci U S A] 2021 Jun 08; Vol. 118 (23). |
| نوع المنشور: | Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't; Research Support, U.S. Gov't, Non-P.H.S. |
| اللغة: | English |
| بيانات الدورية: | Publisher: National Academy of Sciences Country of Publication: United States NLM ID: 7505876 Publication Model: Print Cited Medium: Internet ISSN: 1091-6490 (Electronic) Linking ISSN: 00278424 NLM ISO Abbreviation: Proc Natl Acad Sci U S A Subsets: MEDLINE |
| أسماء مطبوعة: | Original Publication: Washington, DC : National Academy of Sciences |
| مواضيع طبية MeSH: | Bacterial Proteins/*chemistry , Copper/*chemistry , Kynurenine/*chemistry , Metalloproteins/*chemistry , Methylosinus trichosporium/*chemistry, Bacterial Proteins/genetics ; Bacterial Proteins/metabolism ; Copper/metabolism ; Crystallography, X-Ray ; Kynurenine/biosynthesis ; Kynurenine/genetics ; Metalloproteins/genetics ; Metalloproteins/metabolism ; Methylosinus trichosporium/genetics ; Methylosinus trichosporium/metabolism ; Protein Domains |
| مستخلص: | Some methane-oxidizing bacteria use the ribosomally synthesized, posttranslationally modified natural product methanobactin (Mbn) to acquire copper for their primary metabolic enzyme, particulate methane monooxygenase. The operons encoding the machinery to biosynthesize and transport Mbns typically include genes for two proteins, MbnH and MbnP, which are also found as a pair in other genomic contexts related to copper homeostasis. While the MbnH protein, a member of the bacterial diheme cytochrome c peroxidase (bC c P)/MauG superfamily, has been characterized, the structure and function of MbnP, the relationship between the two proteins, and their role in copper homeostasis remain unclear. Biochemical characterization of MbnP from the methanotroph Methylosinus trichosporium OB3b now reveals that MbnP binds a single copper ion, present in the +1 oxidation state, with high affinity. Copper binding to MbnP in vivo is dependent on oxidation of the first tryptophan in a conserved WxW motif to a kynurenine, a transformation that occurs through an interaction of MbnH with MbnP. The 2.04-Å-resolution crystal structure of MbnP reveals a unique fold and an unusual copper-binding site involving a histidine, a methionine, a solvent ligand, and the kynurenine. Although the kynurenine residue may not serve as a Cu I primary-sphere ligand, being positioned ∼2.9 Å away from the Cu I ion, its presence is required for copper binding. Genomic neighborhood analysis indicates that MbnP proteins, and by extension kynurenine-containing copper sites, are widespread and may play diverse roles in microbial copper homeostasis. Competing Interests: The authors declare no competing interest. |
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| معلومات مُعتمدة: | P30 CA060553 United States CA NCI NIH HHS; R01 GM111097 United States GM NIGMS NIH HHS; R35 GM118035 United States GM NIGMS NIH HHS; T32 GM008382 United States GM NIGMS NIH HHS |
| فهرسة مساهمة: | Keywords: MbnP; copper; diheme peroxidase; kynurenine; methanotroph |
| المشرفين على المادة: | 0 (Bacterial Proteins) 0 (Metalloproteins) 343-65-7 (Kynurenine) 789U1901C5 (Copper) |
| تواريخ الأحداث: | Date Created: 20210602 Date Completed: 20211130 Latest Revision: 20211201 |
| رمز التحديث: | 20221213 |
| مُعرف محوري في PubMed: | PMC8201829 |
| DOI: | 10.1073/pnas.2100680118 |
| PMID: | 34074779 |
| قاعدة البيانات: | MEDLINE |
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