6z79 | pdb_00006z79

Variant Surface Glycoprotein VSGsur, I3C ("Magic Triangle") derivative used for phasing of the structure and subsequently as a model for molecular replacement of native, mutants, and drug soaks.

spinqualitylabelsall models 6z79, resolution 1.92Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance. Method: X-ray diffraction, Resolution 1.92Å Ligands: BMA, I3C, MAN, NAG Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT Publication Abstract from PubMed Suramin has been a primary early-stage treatment for African trypanosomiasis for nearly 100 yr. Recent studies revealed that trypanosome strains that express the variant surface glycoprotein (VSG) VSGsur possess heightened resistance to suramin. Here, we show that VSGsur binds tightly to suramin but other VSGs do not. By solving high-resolution crystal structures of VSGsur and VSG13, we also demonstrate that these VSGs define a structurally divergent subgroup of the coat proteins. The co-crystal structure of VSGsur with suramin reveals that the chemically symmetric drug binds within a large cavity in the VSG homodimer asymmetrically, primarily through contacts of its central benzene rings. Structure-based, loss-of-contact mutations in VSGsur significantly decrease the affinity to suramin and lead to a loss of the resistance phenotype. Altogether, these data show that the resistance phenotype is dependent on the binding of suramin to VSGsur, establishing that the VSG proteins can possess functionality beyond their role in antigenic variation. Structure of trypanosome coat protein VSGsur and function in suramin resistance.,Zeelen J, van Straaten M, Verdi J, Hempelmann A, Hashemi H, Perez K, Jeffrey PD, Halg S, Wiedemar N, Maser P, Papavasiliou FN, Stebbins CE Nat Microbiol. 2021 Mar;6(3):392-400. doi: 10.1038/s41564-020-00844-1. Epub 2021 , Jan 18. PMID:33462435 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

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