6edi | pdb_00006edi

Crystal structure of Leishmania braziliensis glucokinase

spinqualitylabelsall models 6edi, resolution 1.85Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 6edi is a 2 chain structure with sequence from Leishmania braziliensis MHOM/BR/75/M2904. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance. Method: X-ray diffraction, Resolution 1.85Å Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT Function A4HPA0_LEIBR Publication Abstract from PubMed Glucokinase from pathogenic protozoa of the genus Leishmania is a potential drug target for the chemotherapeutic treatment against leishmaniasis because this enzyme is located at a nodal point between two critically important metabolic pathways, glycolysis and the pentose phosphate pathway (PPP). L. braziliensis glucokinase (LbGlcK) was evaluated for its structural characterization and enzymatic performance. The enzyme catalyzes the phosphorylation of d-glucose with co-substrate ATP to yield the products G6P and ADP. LbGlcK had KM values determined as 6.61 +/- 2.63 mM and 0.338 +/- 0.080 mM for d-glucose and ATP, respectively. The 1.85 A resolution X-ray crystal structure of the apo form of LbGlcK was determined and a homodimer was revealed where each subunit (both in open conformations) included the typical small and large domains. Structural comparisons were assessed in relationship to Homo sapiens hexokinase IV and Trypanosoma cruzi glucokinase. Comparisons revealed that all residues important for making hydrogen bonding interactions with d-glucose in the active site and catalysis were strictly conserved. LbGlcK was screened against four glucosamine analogue inhibitors and the stronger inhibitor of the series, HPOP-GlcN, had a Ki value of 56.9 +/- 16.6 muM that exhibited competitive inhibition. For the purpose of future structure-based drug design experimentation, L. braziliensis glucokinase was observed to be very similar to T. cruzi glucokinase even though there was a 44% protein sequence identity between the two enzymes. The crystal structure of glucokinase from Leishmania braziliensis.,Buechner GS, Millington ME, Perry K, D'Antonio EL Mol Biochem Parasitol. 2018 Dec 17. pii: S0166-6851(18)30189-0. doi:, 10.1016/j.molbiopara.2018.12.002. PMID:30571993 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See Also Hexokinase 3D structures

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