The human transketolase-like proteins TKTL1 and TKTL2 are bona fide transketolases
Date
2019-01-15
Journal Title
Journal ISSN
Volume Title
Publisher
BMC (part of Springer Nature)
Abstract
Background: 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.
Description
CITATION: 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.
Keywords
Transketolase, Transketolase activity, Transketolase-related genes
Citation
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