6VZZ

Crystal structure of glucokinase from Balamuthia mandrillaris in complex with glucose

Summary for 6VZZ

• Entry DOI: 10.2210/pdb6vzz/pdb
• Descriptor: BamaA.19900.a, beta-D-glucopyranose, CALCIUM ION, ... (5 entities in total)
• Functional Keywords: ssgcid, glucokinase, balamuthia mandrillaris lepto id, structural genomics, seattle structural genomics center for infectious disease, transferase
• Biological source: Balamuthia mandrillaris
• Total number of polymer chains: 1
• Total formula weight: 43574.49

Authors

Seattle Structural Genomics Center for Infectious Disease (SSGCID) (deposition date: 2020-02-28, release date: 2020-03-25, Last modification date: 2023-10-11)

Primary citation

Milanes, J.E.,Suryadi, J.,Monaghan, N.P.,Harding, E.M.,Morris, C.S.,Rozema, S.D.,Khalifa, M.M.,Golden, J.E.,Phan, I.Q.,Zigweid, R.,Abendroth, J.,Rice, C.A.,McCord, H.T.,Wilson, S.,Fenwick, M.K.,Morris, J.C.
Characterization of Glucokinases from Pathogenic Free-Living Amoebae.
Antimicrob.Agents Chemother., :e0237321-e0237321, 2022

PubMed Abstract: Infection with pathogenic free-living amoebae, including Naegleria fowleri, 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 (Glck) as a potential target for therapeutic intervention, as glucose metabolism is critical for viability. Here, we extended these studies to the glucokinases from two other pathogenic free-living amoebae, including Acanthamoeba castellanii (Glck) and (Glck). 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, Glck and Glck have apparent values of 472.5 and 41.0 μM, while Homo sapiens Glck (Glck) has a value of 310 μM. Both parasite enzymes also have a higher apparent affinity for glucose than the human counterpart, with apparent values of 45.9 μM (Glck) and 124 μM (Glck) compared to ~8 mM for Glck. Additionally, Glck and Glck 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.

PubMed: 35604214
DOI: 10.1128/aac.02373-21

Experimental method

X-RAY DIFFRACTION (2.65 Å)