The human transketolase-like proteins TKTL1 and TKTL2 are bona fide transketolases

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dc.contributor.authorDeshpande, Gaurang P.en_ZA
dc.contributor.authorPatterton, Hugh-Georgeen_ZA
dc.contributor.authorFaadiel Essop, M.en_ZA
dc.date.accessioned2019-01-21T05:38:54Z
dc.date.available2019-01-21T05:38:54Z
dc.date.issued2019-01-15
dc.date.updated2019-01-20T04:16:07Z
dc.descriptionCITATION: Deshpande, G. P., Patterton, H. G. & Essop, M. F. 2019. The human transketolase-like proteins TKTL1 and TKTL2 are bona fide transketolases. BMC Structural Biology, 19:2, doi:10.1186/s12900-018-0099-y.
dc.description.abstractBackground: Three transketolase genes have been identified in the human genome to date: transketolase (TKT), transketolase-like 1 (TKTL1) and transketolase-like 2 (TKTL2). Altered TKT functionality is strongly implicated in the development of diabetes and various cancers, thus offering possible therapeutic utility. It will be of great value to know whether TKTL1 and TKTL2 are, similarly, potential therapeutic targets. However, it remains unclear whether TKTL1 and TKTL2 are functional transketolases. Results: Homology modelling of TKTL1 and TKTL2 using TKT as template, revealed that both TKTL1 and TKTL2 could assume a folded structure like TKT. TKTL1/2 presented a cleft of suitable dimensions between the homodimer surfaces that could accommodate the co-factor-substrate. An appropriate cavity and a hydrophobic nodule were also present in TKTL1/2, into which the diphosphate group fitted, and that was implicated in aminopyrimidine and thiazole ring binding in TKT, respectively. The presence of several identical residues at structurally equivalent positions in TKTL1/2 and TKT identified a network of interactions between the protein and co-factor-substrate, suggesting the functional fidelity of TKTL1/2 as transketolases. Conclusions: Our data support the hypothesis that TKTL1 and TKTL2 are functional transketolases and represent novel therapeutic targets for diabetes and cancer.
dc.description.urihttps://bmcstructbiol.biomedcentral.com/articles/10.1186/s12900-018-0099-y
dc.description.versionPublisher's versionen_ZA
dc.format.extent10 pages : illustrationsen_ZA
dc.identifier.citationDeshpande, G. P., Patterton, H. G. & Essop, M. F. 2019. The human transketolase-like proteins TKTL1 and TKTL2 are bona fide transketolases. BMC Structural Biology, 19:2, doi:10.1186/s12900-018-0099-yen_ZA
dc.identifier.issn1472-6807 (online)
dc.identifier.otherdoi:10.1186/s12900-018-0099-y
dc.identifier.urihttp://hdl.handle.net/10019.1/105350
dc.language.isoen_ZAen_ZA
dc.publisherBMC (part of Springer Nature)en_ZA
dc.rights.holderAuthors retain copyrighten_ZA
dc.subjectTransketolaseen_ZA
dc.subjectTransketolase activityen_ZA
dc.subjectTransketolase-related genesen_ZA
dc.titleThe human transketolase-like proteins TKTL1 and TKTL2 are bona fide transketolasesen_ZA
dc.typeArticleen_ZA
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