4itz

Crystal structure of the FK506 binding domain of Plasmodium vivax FKBP35 in complex with a tetrapeptide substrate

spinqualitylabelsall models 4itz, resolution 1.65Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 4itz is a 3 chain structure with sequence from Plasmodium vivax. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance. Method: X-ray diffraction, Resolution 1.65Å Ligands: NIT, SIN, SO4 Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT Function A5K8X6_PLAVS Publication Abstract from PubMed The immunosuppressive drug FK506 binding proteins (FKBPs), an immunophilin family with the immunosuppressive drug FK506 binding property, exhibit peptidylprolyl cis-trans isomerase (PPIase) activity. While the cyclophilin-catalyzed peptidylprolyl isomerization of X-Pro peptide bonds has been extensively studied, the mechanism of the FKBP-mediated peptidylprolyl isomerization still remains uncharacterized. Thus, to investigate the binding of FKBP with its substrate and the underlying catalytic mechanism of the FKBP-mediated proline isomerization, here we employed the FK506 binding domain (FKBD) of the human malarial parasite Plasmodium vivax FK506 binding protein 35 (PvFKBP35) and examined the details of the molecular interaction between the isomerase and a peptide substrate. The crystallographic structures of apo PvFKBD35 and its complex with the tetrapeptide substrate succinyl-Ala-Leu-Pro-Phe-p-nitroanilide (sALPFp) determined at 1.4 A and 1.65 A resolutions, respectively, showed that the substrate binds to PvFKBD35 in a cis conformation. NMR studies demonstrated the chemical shift perturbations of D55, H67, V73 and I74 residues upon the substrate binding. In addition, the X-ray crystal structure along with the mutational studies shows that Y100 is a key residue for the catalytic activity. Taken together, our results provide insights into the catalytic mechanism of PvFKBP35-mediated cis-trans isomerization of substrate and ultimately might aid designing substrate mimetic inhibitors targeting the malarial parasite FKBPs. Structural insights into substrate binding by PvFKBP35, a peptidylprolyl cis-trans isomerase from the human malarial parasite Plasmodium vivax.,Alag R, Balakrishna AM, Rajan S, Qureshi IA, Shin J, Lescar J, Gruber G, Yoon HS Eukaryot Cell. 2013 Feb 22. PMID:23435727 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

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