6vzz

Crystal structure of glucokinase from Balamuthia mandrillaris in complex with glucose

spinqualitylabelsall models 6vzz, resolution 2.65Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 6vzz is a 1 chain structure with sequence from Balamuthia mandrillaris. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance. Method: X-ray diffraction, Resolution 2.65Å Ligands: BGC, CA, EDO Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT Publication Abstract from PubMed Infection with pathogenic free-living amoebae, including Naegleria fowleri, Acanthamoeba spp., and Balamuthia mandrillaris, can lead to life-threatening illnesses, primarily because of catastrophic central nervous system involvement. Efficacious treatment options for these infections are lacking, and the mortality rate due to infection is high. Previously, we evaluated the N. fowleri glucokinase (NfGlck) as a potential target for therapeutic intervention, as glucose metabolism is critical for in vitro viability. Here, we extended these studies to the glucokinases from two other pathogenic free-living amoebae, including Acanthamoeba castellanii (AcGlck) and B. mandrillaris (BmGlck). While these enzymes are similar (49.3% identical at the amino acid level), they have distinct kinetic properties that distinguish them from each other. For ATP, AcGlck and BmGlck have apparent Km values of 472.5 and 41.0 muM, while Homo sapiens Glck (HsGlck) has a value of 310 muM. Both parasite enzymes also have a higher apparent affinity for glucose than the human counterpart, with apparent Km values of 45.9 muM (AcGlck) and 124 muM (BmGlck) compared to ~8 mM for HsGlck. Additionally, AcGlck and BmGlck differ from each other and other Glcks in their sensitivity to small molecule inhibitors, suggesting that inhibitors with pan-amoebic activity could be challenging to generate. Characterization of Glucokinases from Pathogenic Free-Living Amoebae.,Milanes JE, Suryadi J, Monaghan NP, Harding EM, Morris CS, Rozema SD, Khalifa MM, Golden JE, Phan IQ, Zigweid R, Abendroth J, Rice CA, McCord HT, Wilson S, Fenwick MK, Morris JC Antimicrob Agents Chemother. 2022 May 23:e0237321. doi: 10.1128/aac.02373-21. PMID:35604214 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

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