4rph

Crystal structure of Micobacterium tuberculosis UDP-Galactopyranose mutase in complex with substrate UDP-Galp (reduced)

spinqualitylabelsall models 4rph, resolution 2.60Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 4rph is a 3 chain structure with sequence from Mycobacterium tuberculosis H37Rv. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance. Method: X-ray diffraction, Resolution 2.6Å Ligands: FAD, GDU Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT Function GLF_MYCTU Catalyzes the interconversion through a 2-keto intermediate of uridine diphosphogalactopyranose (UDP-GalP) into uridine diphosphogalactofuranose (UDP-GalF) which is a key building block for cell wall construction in Mycobacterium tuberculosis. Publication Abstract from PubMed UDP-Galactopyranose mutase (UGM) is a flavin-containing enzyme that catalyzes the reversible conversion of UDP-galactopyranose (UDP-Galp) to UDP-galactofuranose (UDP-Galf) and plays a key role in the biosynthesis of the mycobacterial cell wall galactofuran. A soluble, active form of UGM from Mycobacterium tuberculosis (MtUGM) was obtained from a dual His6-MBP-tagged MtUGM construct. We present the first complex structures of MtUGM with bound substrate UDP-Galp (both oxidized flavin and reduced flavin). In addition, we have determined the complex structures of MtUGM with inhibitors (UDP and the dideoxy-tetrafluorinated analogues of both UDP-Galp (UDP-F4-Galp) and UDP-Galf (UDP-F4-Galf)), which represent the first complex structures of UGM with an analogue in the furanose form, as well as the first structures of dideoxy-tetrafluorinated sugar analogues bound to a protein. These structures provide detailed insight into ligand recognition by MtUGM and show an overall binding mode similar to those reported for other prokaryotic UGMs. The binding of the ligand induces conformational changes in the enzyme, allowing ligand binding and active-site closure. In addition, the complex structure of MtUGM with UDP-F4-Galf reveals the first detailed insight into how the furanose moiety binds to UGM. In particular, this study confirmed that the furanoside adopts a high-energy conformation (4E) within the catalytic pocket. Moreover, these investigations provide structural insights into the enhanced binding of the dideoxy-tetrafluorinated sugars compared to unmodified analogues. These results will help in the design of carbohydrate mimetics and drug development, and show the enormous possibilities for the use of polyfluorination in the design of carbohydrate mimetics. Structural Basis of Ligand Binding to UDP-Galactopyranose Mutase from Mycobacterium tuberculosis Using Substrate and Tetrafluorinated Substrate Analogues.,van Straaten KE, Kuttiyatveetil JR, Sevrain CM, Villaume SA, Jimenez-Barbero J, Linclau B, Vincent SP, Sanders DA J Am Chem Soc. 2015 Jan 16. PMID:25562380 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See Also UDP-galactopyranose mutase 3D structures

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