Structural basis of terephthalate recognition by solute binding protein TphC
AuthorsGautom, Trishnamoni; orcid: 0000-0001-7602-1228
Dheeman, Dharmendra; orcid: 0000-0002-8933-954X
Alvarez Gonzalez, Guadalupe; orcid: 0000-0003-4387-2231
Le Roy, Philip; orcid: 0000-0002-5496-0272
Caiger, Lewis; orcid: 0000-0001-5156-9684
Fisher, Karl; orcid: 0000-0003-3539-8939
Johannissen, Linus; orcid: 0000-0002-0916-9094
Dixon, Neil; orcid: 0000-0001-9065-6764; email: email@example.com
MetadataShow full item record
AbstractAbstract: Biological degradation of Polyethylene terephthalate (PET) plastic and assimilation of the corresponding monomers ethylene glycol and terephthalate (TPA) into central metabolism offers an attractive route for bio-based molecular recycling and bioremediation applications. A key step is the cellular uptake of the non-permeable TPA into bacterial cells which has been shown to be dependent upon the presence of the key tphC gene. However, little is known from a biochemical and structural perspective about the encoded solute binding protein, TphC. Here, we report the biochemical and structural characterisation of TphC in both open and TPA-bound closed conformations. This analysis demonstrates the narrow ligand specificity of TphC towards aromatic para-substituted dicarboxylates, such as TPA and closely related analogues. Further phylogenetic and genomic context analysis of the tph genes reveals homologous operons as a genetic resource for future biotechnological and metabolic engineering efforts towards circular plastic bio-economy solutions.
CitationNature Communications, volume 12, issue 1, page 6244
PublisherNature Publishing Group UK
DescriptionFrom Springer Nature via Jisc Publications Router
History: received 2021-03-24, accepted 2021-10-06, registration 2021-10-12, pub-electronic 2021-10-29, online 2021-10-29, collection 2021-12
Publication status: Published
Funder: Commonwealth Scholarship Commission (CSC); doi: https://doi.org/10.13039/501100000867; Grant(s): INCN-2018-57
Funder: RCUK | Engineering and Physical Sciences Research Council (EPSRC); doi: https://doi.org/10.13039/501100000266; Grant(s): EP/M013219/1, EP/023755/1
Funder: RCUK | Biotechnology and Biological Sciences Research Council (BBSRC); doi: https://doi.org/10.13039/501100000268; Grant(s): BB/M011208/1, BB/M011208/1, BB/P01738X/1
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No Difference in Penetrance between Truncating and Missense/Aberrant Splicing Pathogenic Variants in MLH1 and MSH2: A Prospective Lynch Syndrome Database StudyDominguez-Valentin, Mev; orcid: 0000-0001-7856-0057; email: Mev.Dominguez.Valentin@rr-research.no; Plazzer, John-Paul; orcid: 0000-0001-5114-4301; email: firstname.lastname@example.org; Sampson, Julian R.; email: Sampson@cardiff.ac.uk; Engel, Christoph; orcid: 0000-0002-7247-282X; email: email@example.com; Aretz, Stefan; orcid: 0000-0002-5228-1890; email: firstname.lastname@example.org; Jenkins, Mark A.; email: email@example.com; Sunde, Lone; email: firstname.lastname@example.org; Bernstein, Inge; email: email@example.com; Capella, Gabriel; orcid: 0000-0002-4669-7320; email: firstname.lastname@example.org; Balaguer, Francesc; orcid: 0000-0002-0206-0539; email: email@example.com; et al. (MDPI, 2021-06-28)Background. Lynch syndrome is the most common genetic predisposition for hereditary cancer. Carriers of pathogenic changes in mismatch repair (MMR) genes have an increased risk of developing colorectal (CRC), endometrial, ovarian, urinary tract, prostate, and other cancers, depending on which gene is malfunctioning. In Lynch syndrome, differences in cancer incidence (penetrance) according to the gene involved have led to the stratification of cancer surveillance. By contrast, any differences in penetrance determined by the type of pathogenic variant remain unknown. Objective. To determine cumulative incidences of cancer in carriers of truncating and missense or aberrant splicing pathogenic variants of the MLH1 and MSH2 genes. Methods. Carriers of pathogenic variants of MLH1 (path_MLH1) and MSH2 (path_MSH2) genes filed in the Prospective Lynch Syndrome Database (PLSD) were categorized as truncating or missense/aberrant splicing according to the InSiGHT criteria for pathogenicity. Results. Among 5199 carriers, 1045 had missense or aberrant splicing variants, and 3930 had truncating variants. Prospective observation years for the two groups were 8205 and 34,141 years, respectively, after which there were no significant differences in incidences for cancer overall or for colorectal cancer or endometrial cancers separately. Conclusion. Truncating and missense or aberrant splicing pathogenic variants were associated with similar average cumulative incidences of cancer in carriers of path MLH1 and path_MSH2.
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