Journal:Acta Cryst D:S2059798324006594
From Proteopedia
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In our study, we have elucidated the crystal structure of GK from T. cruzi, providing critical insights into its function and potential as a drug target. Through comparative sequence analysis, we explored the evolutionary conservation and unique features of this enzyme, which set the stage for a deeper understanding of its role in the parasite's metabolism. Structural analysis allowed a detailed description of the glycerol binding pocket, while superimposition with GK structure from closely related Trypanosoma brucei revealed a strategic location for ATP binding. Notably, the overall fold of the structure, including the dimerization interface, was characterized, highlighting regions crucial for the enzyme's stability and function. | In our study, we have elucidated the crystal structure of GK from T. cruzi, providing critical insights into its function and potential as a drug target. Through comparative sequence analysis, we explored the evolutionary conservation and unique features of this enzyme, which set the stage for a deeper understanding of its role in the parasite's metabolism. Structural analysis allowed a detailed description of the glycerol binding pocket, while superimposition with GK structure from closely related Trypanosoma brucei revealed a strategic location for ATP binding. Notably, the overall fold of the structure, including the dimerization interface, was characterized, highlighting regions crucial for the enzyme's stability and function. | ||
| - | Furthermore, by comparative assessment, we pinpointed a potential regulatory site that may serve as a target for selective inhibition, providing a pathway to design drugs that specifically target the parasite without affecting the host. | + | Furthermore, by comparative assessment, we pinpointed a potential regulatory site that may serve as a target for selective inhibition, providing a pathway to design drugs that specifically target the parasite without affecting the host. Analysis of TcGK structure determined in this study suggests that a comparable regulatory mechanism as seen in ''T. brucei'' Gk (''Tb''GK), may by in place. The spatial orientation of residues Tyr6, Asp23, Lys25, oxCys27 and Asn481 in TcGK resembles the orientation of corresponding residues in TbGK, which latter residues constitute the noncanonical nucleotide binding site. |
Despite our efforts to form a complex with the Pex5 protein, known for its role in peroxisomal protein import, no interaction was observed. This lack of interaction can be attributed to structural constraints, suggesting that the binding sites or conformations required for complex formation are incompatible. This finding emphasizes the specificity of GK interactions and opens avenues for exploring other potential regulatory mechanisms or interacting partners. | Despite our efforts to form a complex with the Pex5 protein, known for its role in peroxisomal protein import, no interaction was observed. This lack of interaction can be attributed to structural constraints, suggesting that the binding sites or conformations required for complex formation are incompatible. This finding emphasizes the specificity of GK interactions and opens avenues for exploring other potential regulatory mechanisms or interacting partners. | ||
Revision as of 14:01, 13 July 2024
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This page complements a publication in scientific journals and is one of the Proteopedia's Interactive 3D Complement pages. For aditional details please see I3DC.
