3wxi | pdb_00003wxi

Crystal structure of trypanosoma brucei gambiense glycerol kinase (ligand-free form)

spinqualitylabelsall models 3wxi, resolution 2.90Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 3wxi is a 2 chain structure with sequence from Trypanosoma brucei gambiense. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance. Method: X-ray diffraction, Resolution 2.9Å Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT Function D3KVM3_TRYBG Publication Abstract from PubMed The glycerol kinase (GK) of African human trypanosomes is compartmentalized in their glycosomes. Unlike the host GK, which under physiological conditions catalyzes only the forward reaction (ATP-dependent glycerol phosphorylation), trypanosome GK can additionally catalyze the reverse reaction. In fact, owing to this unique reverse catalysis, GK is potentially essential for the parasites survival in the human host, hence a promising drug target. The mechanism of its reverse catalysis was unknown; therefore, it was not clear if this ability was purely due to its localization in the organelles or whether structure-based catalytic differences also contribute. To investigate this lack of information, the X-ray crystal structure of this protein was determined up to 1.90 A resolution, in its unligated form and in complex with three natural ligands. These data, in conjunction with results from structure-guided mutagenesis suggests that the trypanosome GK is possibly a transiently autophosphorylating threonine kinase, with the catalytic site formed by non-conserved residues. Our results provide a series of structural peculiarities of this enzyme, and gives unexpected insight into the reverse catalysis mechanism. Together, they provide an encouraging molecular framework for the development of trypanosome GK-specific inhibitors, which may lead to the design of new and safer trypanocidal drug(s). Molecular basis for the reverse reaction of African human trypanosomes glycerol kinase.,Balogun EO, Inaoka DK, Shiba T, Kido Y, Tsuge C, Nara T, Aoki T, Honma T, Tanaka A, Inoue M, Matsuoka S, Michels PA, Kita K, Harada S Mol Microbiol. 2014 Dec;94(6):1315-29. doi: 10.1111/mmi.12831. Epub 2014 Nov 4. PMID:25315291 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See Also Glycerol kinase

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