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| [PMID]: | 28461332 |
| [Au] Autor: | Temple MJ; Cuskin F; Baslé A; Hickey N; Speciale G; Williams SJ; Gilbert HJ; Lowe EC |
| [Ad] Endereço: | From the Institute of Cell and Molecular Biosciences, Newcastle University, Newcastle upon Tyne NE4 2HH, United Kingdom and. |
| [Ti] Título: | A Bacteroidetes locus dedicated to fungal 1,6-ß-glucan degradation: Unique substrate conformation drives specificity of the key endo-1,6-ß-glucanase. |
| [So] Source: | J Biol Chem;292(25):10639-10650, 2017 06 23. | | [Is] ISSN: | 1083-351X |
| [Cp] País de publicação: | United States |
| [La] Idioma: | eng |
| [Ab] Resumo: | Glycans are major nutrients available to the human gut microbiota. The are generalist glycan degraders, and this function is mediated largely by polysaccharide utilization loci (PULs). The genomes of several species contain a PUL, PUL , that was predicted to target mixed linked plant 1,3;1,4-ß-glucans. To test this hypothesis we characterized the proteins encoded by this locus in , a member of the human gut microbiota. We show here that PUL does not orchestrate the degradation of a plant polysaccharide but targets a fungal cell wall glycan, 1,6-ß-glucan, which is a growth substrate for the bacterium. The locus is up-regulated by 1,6-ß-glucan and encodes two enzymes, a surface endo-1,6-ß-glucanase, BT3312, and a periplasmic ß-glucosidase that targets primarily 1,6-ß-glucans. The non-catalytic proteins encoded by PUL target 1,6-ß-glucans and comprise a surface glycan-binding protein and a SusD homologue that delivers glycans to the outer membrane transporter. We identified the central role of the endo-1,6-ß-glucanase in 1,6-ß-glucan depolymerization by deleting , which prevented the growth of on 1,6-ß-glucan. The crystal structure of BT3312 in complex with ß-glucosyl-1,6-deoxynojirimycin revealed a TIM barrel catalytic domain that contains a deep substrate-binding cleft tailored to accommodate the hook-like structure adopted by 1,6-ß-glucan. Specificity is driven by the complementarity of the enzyme active site cleft and the conformation of the substrate. We also noted that PUL is syntenic to many PULs from other Bacteroidetes, suggesting that utilization of yeast and fungal cell wall 1,6-ß-glucans is a widespread adaptation within the human microbiota. |
| [Mh] Termos MeSH primário: |
Proteínas de Bactérias/química
Bacteroidetes/enzimologia
Polissacarídeos Fúngicos/química
Glicosídeo Hidrolases/química
beta-Glucanas/química
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| [Mh] Termos MeSH secundário: |
Proteínas de Bactérias/genética
Bacteroidetes/genética
Configuração de Carboidratos
Cristalografia por Raios X
Loci Gênicos
Glicosídeo Hidrolases/genética
Seres Humanos
Especificidade por Substrato
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| [Pt] Tipo de publicação: | JOURNAL ARTICLE; RESEARCH SUPPORT, NON-U.S. GOV'T |
[Nm] Nome de substância:
| 0 (Bacterial Proteins); 0 (Fungal Polysaccharides); 0 (beta-Glucans); EC 3.2.1.- (Glycoside Hydrolases); EC 3.2.1.75 (endo-1,6-beta-glucanase) |
| [Em] Mês de entrada: | 1707 |
| [Cu] Atualização por classe: | 171229 |
[Lr] Data última revisão:
| 171229 |
| [Sb] Subgrupo de revista: | IM |
| [Da] Data de entrada para processamento: | 170503 |
| [St] Status: | MEDLINE |
| [do] DOI: | 10.1074/jbc.M117.787606 |
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